Integration of Biochemical and Mechanical Signals at the Nuclear Periphery: Impacts on Skin Development and Disease

  • Rachel M. Stewart
  • Megan C. KingEmail author
  • Valerie HorsleyEmail author
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


During skin development and keratinocyte differentiation, the nucleus undergoes characteristic changes in shape, size, and transcriptional output. Many of these changes are regulated by the interface between the nuclear interior and the inner nuclear membrane, a region called the nuclear lamina. The nuclear lamina is composed of a meshwork of the nuclear lamins, which interact with integral inner nuclear membrane proteins, and the associated chromatin. Studies in the last decade have revealed a view of the nuclear lamina as a hub for biochemical and mechanical inputs. In this chapter, we will discuss how the structure and organization of the nucleus allows biochemical and mechanical signals to regulate gene expression, genome integrity, cell and tissue level mechanics, and disease in the context of skin homeostasis and regeneration.


Nuclear envelope LINC complex Lamina Skin Mechanics 



Adherens junctions


Adenomatous polyposis coli


Barrier-to-autointegration factor


Chromatin immunoprecipitation sequencing


DNA damage response


Double-strand break


Extracellular Matrix


Epidermal differentiation complex

GA repeat

Guanine-adenine repeat


Di- or trimethylation of lysine 9 on histone H2


Trimethylation of lysine 27 on histone H3


Histone deacetylase


Hutchinson-Gilford Progeria Syndrome


High-throughput chromosome capture


Interfollicular epidermis


Inner nuclear membrane


LAP2, emerin and MAN1


Outer nuclear membrane


Lamina associated domain


Lamina-associated polypeptide 1


Lamina-associated polypeptide 2


Lamin B receptor


Linker of Nucleoskeleton and Cytoskeleton


Mouse embryonic fibroblast


Arginylglycylaspartic acid

TAN lines

Transmembrane actin-associated nuclear lines


  1. 1.
    Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005;6:328–40. Scholar
  2. 2.
    Blanpain C, Fuchs E. Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol. 2009;10:207–17. Scholar
  3. 3.
    Lechler T, Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature. 2005;437:275–80. Scholar
  4. 4.
    Koster MI, Roop DR. Asymmetric cell division in skin development: a new look at an old observation. Dev Cell. 2005;9:444–6. Scholar
  5. 5.
    Simpson CL, Patel DM, Green KJ. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol. 2011;12:565–80. Scholar
  6. 6.
    Delva E, Tucker DK, Kowalczyk AP. The desmosome. Cold Spring Harb Perspect Biol. 2009;1:a002543. Scholar
  7. 7.
    Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002;156:1099–111. Scholar
  8. 8.
    Morita K, Itoh M, Saitou M, Ando-Akatsuka Y, Furuse M, Yoneda K, Imamura S, Fujimoto K, Tsukita S. Subcellular distribution of tight junction-associated proteins (occludin, ZO-1, ZO-2) in rodent skin. J Invest Dermatol. 1998;110:862–6. Scholar
  9. 9.
    Schlüter H, Wepf R, Moll I, Franke WW. Sealing the live part of the skin: the integrated meshwork of desmosomes, tight junctions and curvilinear ridge structures in the cells of the uppermost granular layer of the human epidermis. Eur J Cell Biol. 2004;83:655–65. Scholar
  10. 10.
    Gdula MR, Poterlowicz K, Mardaryev AN, Sharov AA, Peng Y, Fessing MY, Botchkarev VA. Remodeling of three-dimensional organization of the nucleus during terminal keratinocyte differentiation in the epidermis. J Invest Dermatol. 2013;133:2191–201. Scholar
  11. 11.
    Burke B, Stewart CL. The nuclear lamins: flexibility in function. Nat Rev Mol Cell Biol. 2013;14:13–24. Scholar
  12. 12.
    Chang W, Worman HJ, Gundersen GG. Accessorizing and anchoring the LINC complex for multifunctionality. J Cell Biol. 2015;208:11–22. Scholar
  13. 13.
    Peter A, Stick R. Evolutionary aspects in intermediate filament proteins. Curr Opin Cell Biol. 2015;32:48–55. Scholar
  14. 14.
    Heitlinger E, Peter M, Lustig A, Villiger W, Nigg EA, Aebi U. The role of the head and tail domain in lamin structure and assembly: analysis of bacterially expressed chicken lamin A and truncated B2 lamins. J Struct Biol. 1992;108:74–89.CrossRefPubMedGoogle Scholar
  15. 15.
    Herrmann H, Aebi U. Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular Scaffolds. Annu Rev Biochem. 2004;73:749–89. Scholar
  16. 16.
    Gruenbaum Y, Medalia O. Lamins: the structure and protein complexes. Curr Opin Cell Biol. 2015;32:7–12. Scholar
  17. 17.
    Turgay Y, Eibauer M, Goldman AE, Shimi T, Khayat M, Ben-Harush K, Dubrovsky-Gaupp A, Sapra KT, Goldman RD, Medalia O. The molecular architecture of lamins in somatic cells. Nature. 2017;543:261–4. Scholar
  18. 18.
    Shimi T, Kittisopikul M, Tran J, Goldman AE, Adam SA, Zheng Y, Jaqaman K, Goldman RD. Structural organization of nuclear lamins A, C, B1 and B2 revealed by super-resolution microscopy. Mol Biol Cell. 2015;26(22):4075–86. Scholar
  19. 19.
    Xie W, Chojnowski A, Boudier T, Lim JSY, Ahmed S, Ser Z, Stewart C, Burke B. A-type Lamins form distinct filamentous networks with differential nuclear pore complex associations. Curr Biol. 2016;26:2651–8. Scholar
  20. 20.
    Worman HJ, Lazaridis I, Georgatos SD. Nuclear lamina heterogeneity in mammalian cells. Differential expression of the major lamins and variations in lamin B phosphorylation. J Biol Chem. 1988;263:12135–41.PubMedGoogle Scholar
  21. 21.
    Constantinescu D, Gray HL, Sammak PJ, Schatten GP, Csoka AB. Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation. Stem Cells. 2006;24:177–85. Scholar
  22. 22.
    Swift J, Ivanovska IL, Buxboim A, Harada T, Dingal PCDP, Pinter J, Pajerowski JD, Spinler KR, Shin J-W, Tewari M, Rehfeldt F, Speicher DW, Discher DE. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science. 2013;341:1240104. Scholar
  23. 23.
    Shin J-W, Spinler KR, Swift J, Chasis JA, Mohandas N, Discher DE. Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells. Proc Natl Acad Sci USA. 2013;110:18892–7. Scholar
  24. 24.
    Venables RS, McLean S, Luny D, Moteleb E, Morley S, Quinlan RA, Lane EB, Hutchison CJ. Expression of individual lamins in basal cell carcinomas of the skin. Br J Cancer. 2001;84:512–9. Scholar
  25. 25.
    Hanif M, Rosengardten Y, Sagelius H, Rozell B, Eriksson M. Differential expression of A-type and B-type lamins during hair cycling. PLoS One. 2009;4:e4114. Scholar
  26. 26.
    Rusiñol AE, Sinensky MS. Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J Cell Sci. 2006;119:3265–72. Scholar
  27. 27.
    De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Lévy N. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003;300:2055. Scholar
  28. 28.
    Solovei II, Wang ASA, Thanisch KK, Schmidt CSC, Krebs SS, Zwerger MM, Cohen TVT, Devys DD, Foisner RR, Peichl LL, Herrmann HH, Blum HH, Engelkamp DD, Stewart CLC, Leonhardt HH, Joffe BB. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell. 2013;152:584–98.CrossRefPubMedGoogle Scholar
  29. 29.
    McKenna T, Rosengardten Y, Viceconte N, Baek J-H, Grochová D, Eriksson M. Embryonic expression of the common progeroid lamin A splice mutation arrests postnatal skin development. Aging Cell. 2014;13:292–302. Scholar
  30. 30.
    Jung H-J, Tatar A, Tu Y, Nobumori C, Yang SH, Goulbourne CN, Herrmann H, Fong LG, Young SG. An absence of nuclear lamins in keratinocytes leads to ichthyosis, defective epidermal barrier function, and intrusion of nuclear membranes and endoplasmic reticulum into the nuclear chromatin. Mol Cell Biol. 2014;34:4534–44. Scholar
  31. 31.
    Ihalainen TO, Aires L, Herzog FA, Schwartlander R, Moeller J, Vogel V. Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension. Nat Mater. 2015.
  32. 32.
    Naeem AS, Zhu Y, Di WL, Marmiroli S, O'Shaughnessy RFL. AKT1-mediated Lamin A/C degradation is required for nuclear degradation and normal epidermal terminal differentiation. Cell Death Differ. 2015.
  33. 33.
    Wallace L, Roberts-Thompson L, Reichelt J. Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity. J Cell Sci. 2012;125:1750–8. Scholar
  34. 34.
    Barton LJ, Soshnev AA, Geyer PK. Networking in the nucleus: a spotlight on LEM-domain proteins. Curr Opin Cell Biol. 2015;34:1–8. Scholar
  35. 35.
    Shin J-Y, Dauer WT, Worman HJ. Lamina-associated polypeptide 1: protein interactions and tissue-selective functions. Semin Cell Dev Biol. 2014;29:164–8. Scholar
  36. 36.
    Gesson K, Vidak S, Foisner R. Lamina-associated polypeptide (LAP)2α and nucleoplasmic lamins in adult stem cell regulation and disease. Semin Cell Dev Biol. 2014;29:116–24. Scholar
  37. 37.
    Olins AL, Rhodes G, Welch DBM, Zwerger M, Olins DE. Lamin B receptor: multi-tasking at the nuclear envelope. Nucleus. 2010;1:53–70. Scholar
  38. 38.
    Dauer WT, Worman HJ. The nuclear envelope as a signaling node in development and disease. Dev Cell. 2009;17:626–38. Scholar
  39. 39.
    Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol. 2009;10:75–82. Scholar
  40. 40.
    Maniotis AJ, Ingber DE, Chen CS. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci USA. 1997;94:849–54.CrossRefPubMedGoogle Scholar
  41. 41.
    Buxboim A, Swift J, Irianto J, Spinler KR, Dingal PCDP, Athirasala A, Kao Y-RC, Cho S, Harada T, Shin J-W, Discher DE. Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin. Curr Biol. 2014;24:1909–17. Scholar
  42. 42.
    Poh Y-C, Shevtsov SP, Chowdhury F, Wu DC, Na S, Dundr M, Wang N. Dynamic force-induced direct dissociation of protein complexes in a nuclear body in living cells. Nat Commun. 2012;3:866. Scholar
  43. 43.
    Booth-Gauthier EA, Alcoser TA, Yang G, Dahl KN. Force-induced changes in subnuclear movement and rheology. Biophys J. 2012;103:2423–31. Scholar
  44. 44.
    Lombardi ML, Jaalouk DE, Shanahan CM, Burke B, Roux KJ, Lammerding J. The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton. J Biol Chem. 2011;286:26743–53. Scholar
  45. 45.
    Chambliss AB, Khatau SB, Erdenberger N, Robinson DK, Hodzic D, Longmore GD, Wirtz D. The LINC-anchored actin cap connects the extracellular milieu to the nucleus for ultrafast mechanotransduction. Sci Rep. 2013;3:1087. Scholar
  46. 46.
    Guilluy C, Osborne LD, Van Landeghem L, Sharek L, Superfine R, Garcia-Mata R, Burridge K. Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nat Cell Biol. 2014;16:376–81. Scholar
  47. 47.
    Morgan JT, Pfeiffer ER, Thirkill TL, Kumar P, Peng G, Fridolfsson HN, Douglas GC, Starr DA, Barakat AI. Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization. Mol Biol Cell. 2011;22:4324–34. Scholar
  48. 48.
    Gundersen GG, Worman HJ. Nuclear positioning. Cell. 2013;152:1376–89. Scholar
  49. 49.
    Thakar K, May CK, Rogers A, Carroll CW. Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA. Mol Biol Cell. 2017;28:182–91. Scholar
  50. 50.
    Mounkes LC, Kozlov SV, Rottman JN, Stewart CL. Expression of an LMNA-N195K variant of A-type lamins results in cardiac conduction defects and death in mice. Hum Mol Genet. 2005;14:2167–80. Scholar
  51. 51.
    Frock RL, Chen SC, Da D-F, Frett E, Lau C, Brown C, Pak DN, Wang Y, Muchir A, Worman HJ, Santana LF, Ladiges WC, Rabinovitch PS, Kennedy BK. Cardiomyocyte-specific expression of lamin a improves cardiac function in Lmna-/- mice. PLoS One. 2012;7:e42918. Scholar
  52. 52.
    Hale CM, Shrestha AL, Khatau SB, Stewart-Hutchinson PJ, Hernandez L, Stewart CL, Hodzic D, Wirtz D. Dysfunctional connections between the nucleus and the actin and microtubule networks in laminopathic models. Biophys J. 2008;95:5462–75. Scholar
  53. 53.
    Lee JSH, Hale CM, Panorchan P, Khatau SB, George JP, Tseng Y, Stewart CL, Hodzic D, Wirtz D. Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration. Biophys J. 2007;93:2542–52. Scholar
  54. 54.
    Kim D-H, Khatau SB, Feng Y, Walcott S, Sun SX, Longmore GD, Wirtz D. Actin cap associated focal adhesions and their distinct role in cellular mechanosensing. Sci Rep. 2012;2:555. Scholar
  55. 55.
    Dupin I, Camand E, Etienne-Manneville S. Classical cadherins control nucleus and centrosome position and cell polarity. J Cell Biol. 2009;185:779–86. Scholar
  56. 56.
    Stewart RM, Zubek AE, Rosowski KA, Schreiner SM, Horsley V, King MC. Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions. J Cell Biol. 2015;209:403–18. Scholar
  57. 57.
    Lammerding J, Fong LG, Ji JY, Reue K, Stewart CL, Young SG, Lee RT. Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem. 2006;281:25768–80. Scholar
  58. 58.
    Trappmann B, Gautrot JE, Connelly JT, Strange DGT, Li Y, Oyen ML, Cohen Stuart MA, Boehm H, Li B, Vogel V, Spatz JP, Watt FM, Huck WTS. Extracellular-matrix tethering regulates stem-cell fate. Nat Mater. 2012;11:642–9. Scholar
  59. 59.
    Schreiner SM, Koo PK, Zhao Y, Mochrie SGJ, King MC. The tethering of chromatin to the nuclear envelope supports nuclear mechanics. Nat Commun. 2015;6:7159. Scholar
  60. 60.
    Dahl KN, Kahn SM, Wilson KL, Discher DE. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J Cell Sci. 2004;117:4779–86. Scholar
  61. 61.
    Stephens AD, Banigan EJ, Adam SA, Goldman RD, Marko JF. Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus. Mol Biol Cell. 2017;28:1984–96. Scholar
  62. 62.
    Furusawa T, Rochman M, Taher L, Dimitriadis EK, Nagashima K, Anderson S, Bustin M. Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness. Nat Commun. 2015;6:6138. Scholar
  63. 63.
    Gerlitz G, Bustin M. Efficient cell migration requires global chromatin condensation. J Cell Sci. 2010;123:2207–17. Scholar
  64. 64.
    Chubb JR, Boyle S, Perry P, Bickmore WA. Chromatin motion is constrained by association with nuclear compartments in human cells. Curr Biol. 2002;12:439–45.CrossRefPubMedGoogle Scholar
  65. 65.
    Bronshtein I, Kepten E, Kanter I, Berezin S, Lindner M, Redwood AB, Mai S, Gonzalo S, Foisner R, Shav-Tal Y, Garini Y. Loss of lamin A function increases chromatin dynamics in the nuclear interior. Nat Commun. 2015;6:8044. Scholar
  66. 66.
    Luxton GWG, Gomes ER, Folker ES, Vintinner E, Gundersen GG. Linear arrays of nuclear envelope proteins harness retrograde actin flow for nuclear movement. Science. 2010;329:956–9. Scholar
  67. 67.
    Lei K, Zhu X, Xu R, Shao C, Xu T, Zhuang Y, Han M. Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA damage response. Curr Biol. 2012;22:1609–15. Scholar
  68. 68.
    Harada T, Swift J, Irianto J, Shin J-W, Spinler KR, Athirasala A, Diegmiller R, Dingal PCDP, Ivanovska IL, Discher DE. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J Cell Biol. 2014;204:669–82. Scholar
  69. 69.
    Mattout A, Pike BL, Towbin BD, Bank EM, Gonzalez-Sandoval A, Stadler MB, Meister P, Gruenbaum Y, Gasser SM. An EDMD mutation in C. elegans lamin blocks muscle-specific gene relocation and compromises muscle integrity. Curr Biol. 2011;21:1603–14. Scholar
  70. 70.
    Towbin BD, Meister P, Pike BL, Gasser SM. Repetitive transgenes in C. elegans accumulate heterochromatic marks and are sequestered at the nuclear envelope in a copy-number- and lamin-dependent manner. Cold Spring Harb Symp Quant Biol. 2010;75:555–65. Scholar
  71. 71.
    Guelen L, Pagie L, Brasset E, Meuleman W, Faza MB, Talhout W, Eussen BH, de Klein A, Wessels L, de Laat W, van Steensel B. Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature. 2008;453:948–51. Scholar
  72. 72.
    Harr JC, Luperchio TR, Wong X, Cohen E, Wheelan SJ, Reddy KL. Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins. J Cell Biol. 2015;208:33–52. Scholar
  73. 73.
    Zullo JM, Demarco IA, Piqué-Regi R, Gaffney DJ, Epstein CB, Spooner CJ, Luperchio TR, Bernstein BE, Pritchard JK, Reddy KL, Singh H. DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina. Cell. 2012;149:1474–87. Scholar
  74. 74.
    Towbin BD, González-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P, Askjaer P, Gasser SM. Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery. Cell. 2012;150:934–47. Scholar
  75. 75.
    Kind J, Pagie L, Ortabozkoyun H, Boyle S, de Vries SS, Janssen H, Amendola M, Nolen LD, Bickmore WA, van Steensel B. Single-cell dynamics of genome-nuclear lamina interactions. Cell. 2013;153:178–92. Scholar
  76. 76.
    Kumaran RI, Spector DL. A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J Cell Biol. 2008;180:51–65. Scholar
  77. 77.
    Reddy KL, Zullo JM, Bertolino E, Singh H. Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature. 2008;452:243–7. Scholar
  78. 78.
    Van de Vosse DW, Wan Y, Wozniak RW, Aitchison JD. Role of the nuclear envelope in genome organization and gene expression. Wiley Interdiscip Rev Syst Biol Med. 2011;3:147–66. Scholar
  79. 79.
    Kubben N, Adriaens M, Meuleman W, Voncken JW, van Steensel B, Misteli T. Mapping of lamin A- and progerin-interacting genome regions. Chromosoma. 2012;121:447–64. Scholar
  80. 80.
    Demmerle J, Koch AJ, Holaska JM. The nuclear envelope protein emerin binds directly to histone deacetylase 3 (HDAC3) and activates HDAC3 activity. J Biol Chem. 2012;287:22080–8. Scholar
  81. 81.
    Nagano T, Lubling Y, Stevens TJ, Schoenfelder S, Yaffe E, Dean W, Laue ED, Tanay A, Fraser P. Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature. 2013;502:59–64. Scholar
  82. 82.
    Andrés V, González JM. Role of A-type lamins in signaling, transcription, and chromatin organization. J Cell Biol. 2009;187:945–57. Scholar
  83. 83.
    Kypriotou M, Huber M, Hohl D. The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the “fused genes” family. Exp Dermatol. 2012;21:643–9. Scholar
  84. 84.
    Williams RRE, Broad S, Sheer D, Ragoussis J. Subchromosomal positioning of the epidermal differentiation complex (EDC) in keratinocyte and lymphoblast interphase nuclei. Exp Cell Res. 2002;272:163–75. Scholar
  85. 85.
    Mardaryev AN, Gdula MR, Yarker JL, Emelianov VU, Emelianov VN, Poterlowicz K, Sharov AA, Sharova TY, Scarpa JA, Joffe B, Solovei I, Chambon P, Botchkarev VA, Fessing MY. p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells. Development. 2014;141:101–11. Scholar
  86. 86.
    Fessing MY, Mardaryev AN, Gdula MR, Sharov AA, Sharova TY, Rapisarda V, Gordon KB, Smorodchenko AD, Poterlowicz K, Ferone G, Kohwi Y, Missero C, Kohwi-Shigematsu T, Botchkarev VA. p63 regulates Satb1 to control tissue-specific chromatin remodeling during development of the epidermis. J Cell Biol. 2011;194:825–39. Scholar
  87. 87.
    Lien W-H, Guo X, Polak L, Lawton LN, Young RA, Zheng D, Fuchs E. Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage. Cell Stem Cell. 2011;9:219–32. Scholar
  88. 88.
    Indra AK, Dupé V, Bornert J-M, Messaddeq N, Yaniv M, Mark M, Chambon P, Metzger D. Temporally controlled targeted somatic mutagenesis in embryonic surface ectoderm and fetal epidermal keratinocytes unveils two distinct developmental functions of BRG1 in limb morphogenesis and skin barrier formation. Development. 2005;132:4533–44. Scholar
  89. 89.
    Kashiwagi M, Morgan BA, Georgopoulos K. The chromatin remodeler Mi-2beta is required for establishment of the basal epidermis and normal differentiation of its progeny. Development. 2007;134:1571–82. Scholar
  90. 90.
    LeBoeuf M, Terrell A, Trivedi S, Sinha S, Epstein JA, Olson EN, Morrisey EE, Millar SE. Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell. 2010;19:807–18. Scholar
  91. 91.
    Frye M, Fisher AG, Watt FM. Epidermal stem cells are defined by global histone modifications that are altered by Myc-induced differentiation. PLoS One. 2007;2:e763. Scholar
  92. 92.
    Hughes MW, Jiang T-X, Lin S-J, Leung Y, Kobielak K, Widelitz RB, Chuong CM. Disrupted ectodermal organ morphogenesis in mice with a conditional histone deacetylase 1, 2 deletion in the epidermis. J Invest Dermatol. 2014;134:24–32. Scholar
  93. 93.
    Rapisarda V, Malashchuk I, Asamaowei IE, Poterlowicz K, Fessing MY, Sharov AA, Karakesisoglou I, Botchkarev VA, Mardaryev A. p63 transcription factor regulates nuclear shape and expression of nuclear envelope-associated genes in epidermal keratinocytes. J Invest Dermatol. 2017.
  94. 94.
    Ivorra C, Kubicek M, González JM, Sanz-González SM, Alvarez-Barrientos A, O'Connor J-E, Burke B, Andrés V. A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C. Genes Dev. 2006;20:307–20. Scholar
  95. 95.
    González JM, Navarro-Puche A, Casar B, Crespo P, Andrés V. Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope. J Cell Biol. 2008;183:653–66. Scholar
  96. 96.
    Oh IY, Albea DM, Goodwin ZA, Quiggle AM, Baker BP, Guggisberg AM, Geahlen JH, Kroner GM, de Guzman Strong C. Regulation of the dynamic chromatin architecture of the epidermal differentiation complex is mediated by a c-Jun/AP-1-modulated enhancer. J Invest Dermatol. 2014;134:2371–80. Scholar
  97. 97.
    Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su I-H, Hannon G, Tarakhovsky A, Fuchs E. Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell. 2009;136:1122–35. Scholar
  98. 98.
    Blanpain C, Fuchs E. Epidermal stem cells of the skin. Annu Rev Cell Dev Biol. 2006;22:339–73. Scholar
  99. 99.
    Markiewicz E, Tilgner K, Barker N, van de Wetering M, Clevers H, Dorobek M, Hausmanowa-Petrusewicz I, Ramaekers FCS, Broers JLV, Blankesteijn WM, Salpingidou G, Wilson RG, Ellis JA, Hutchison CJ. The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO J. 2006;25:3275–85. Scholar
  100. 100.
    Tilgner K, Wojciechowicz K, Jahoda C, Hutchison C, Markiewicz E. Dynamic complexes of A-type lamins and emerin influence adipogenic capacity of the cell via nucleocytoplasmic distribution of beta-catenin. J Cell Sci. 2009;122:401–13. Scholar
  101. 101.
    Stubenvoll A, Rice M, Wietelmann A, Wheeler M, Braun T. Attenuation of Wnt/β-catenin activity reverses enhanced generation of cardiomyocytes and cardiac defects caused by the loss of emerin. Hum Mol Genet. 2015;24:802–13. Scholar
  102. 102.
    Neumann S, Schneider M, Daugherty RL, Gottardi CJ, Eming SA, Beijer A, Noegel AA, Karakesisoglou I. Nesprin-2 interacts with {alpha}-catenin and regulates Wnt signaling at the nuclear envelope. J Biol Chem. 2010;285:34932–8. Scholar
  103. 103.
    Lim X, Nusse R. Wnt signaling in skin development, homeostasis, and disease. Cold Spring Harb Perspect Biol. 2013;5:a008029. Scholar
  104. 104.
    Lin F, Morrison JM, Wu W, Worman HJ. MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. Hum Mol Genet. 2005;14:437–45. Scholar
  105. 105.
    Bengtsson L. What MAN1 does to the Smads. TGFbeta/BMP signaling and the nuclear envelope. FEBS J. 2007;274:1374–82.CrossRefPubMedGoogle Scholar
  106. 106.
    Hellemans J, Preobrazhenska O, Willaert A, Debeer P, Verdonk PCM, Costa T, Janssens K, Menten B, Van Roy N, Vermeulen SJT, Savarirayan R, Van Hul W, Vanhoenacker F, Huylebroeck D, De Paepe A, Naeyaert J-M, Vandesompele J, Speleman F, Verschueren K, Coucke PJ, Mortier GR. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet. 2004. Published online: 10 December 2001; doi:101038/ng789 36:1213–18. doi:
  107. 107.
    Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K. Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts. J Clin Invest. 2004;113:253–64. Scholar
  108. 108.
    Mori Y, Chen S-J, Varga J. Expression and regulation of intracellular SMAD signaling in scleroderma skin fibroblasts. Arthritis Rheum. 2003;48:1964–78. Scholar
  109. 109.
    Rashmi RN, Eckes B, Glöckner G, Groth M, Neumann S, Gloy J, Sellin L, Walz G, Schneider M, Karakesisoglou I, Eichinger L, Noegel AA. The nuclear envelope protein Nesprin-2 has roles in cell proliferation and differentiation during wound healing. Nucleus. 2012;3:172–86. Scholar
  110. 110.
    Mayr M, Hu Y, Hainaut H, Xu Q. Mechanical stress-induced DNA damage and rac-p38MAPK signal pathways mediate p53-dependent apoptosis in vascular smooth muscle cells. FASEB J. 2002;16:1423–5. Scholar
  111. 111.
    Lawrence KS, Tapley EC, Cruz VE, Li Q, Aung K, Hart KC, Schwartz TU, Starr DA, Engebrecht J. LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining. J Cell Biol. 2016;215:801–21. Scholar
  112. 112.
    Sur I, Neumann S, Noegel AA. Nesprin-1 role in DNA damage response. Nucleus. 2014;5:173–91. Scholar
  113. 113.
    Warren DT, Tajsic T, Porter LJ, Minaisah RM, Cobb A, Jacob A, Rajgor D, Zhang QP, Shanahan CM. Nesprin-2-dependent ERK1/2 compartmentalisation regulates the DNA damage response in vascular smooth muscle cell ageing. Cell Death Differ. 2015;22:1540–50. Scholar
  114. 114.
    Oza P, Jaspersen SL, Miele A, Dekker J, Peterson CL. Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev. 2009;23:912–27. Scholar
  115. 115.
    Kalocsay M, Hiller NJ, Jentsch S. Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol Cell. 2009;33:335–43. Scholar
  116. 116.
    Swartz RK, Rodriguez EC, King MC. A role for nuclear envelope-bridging complexes in homology-directed repair. Mol Biol Cell. 2014;25:2461–71. Scholar
  117. 117.
    Kubben N, Voncken JW, Demmers J, Calis C, van Almen G, Pinto Y, Misteli T. Identification of differential protein interactors of lamin A and progerin. Nucleus. 2010;1:513–25. Scholar
  118. 118.
    Gonzalez-Suarez I, Gonzalo S. Nurturing the genome: A-type lamins preserve genomic stability. Nucleus. 2010;1:129–35. Scholar
  119. 119.
    Gonzalo S. DNA damage and lamins. Adv Exp Med Biol. 2014;773:377–99. Scholar
  120. 120.
    Manju K, Muralikrishna B, Parnaik VK. Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. J Cell Sci. 2006;119:2704–14. Scholar
  121. 121.
    Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang J-D, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadiñanos J, López-Otín C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KSE, Tryggvason K, Zhou Z. Genomic instability in laminopathy-based premature aging. Nat Med. 2005;11:780–5. Scholar
  122. 122.
    Mahen R, Hattori H, Lee M, Sharma P, Jeyasekharan AD, Venkitaraman AR. A-type lamins maintain the positional stability of DNA damage repair foci in mammalian nuclei. PLoS One. 2013;8:e61893. Scholar
  123. 123.
    Starke S, Meinke P, Camozzi D, Mattioli E, Pfaeffle R, Siekmeyer M, Hirsch W, Horn LC, Paasch U, Mitter D, Lattanzi G, Wehnert M, Kiess W. Progeroid laminopathy with restrictive dermopathy-like features caused by an isodisomic LMNA mutation p.R435C. Aging (Albany NY). 2013;5:445–59.CrossRefGoogle Scholar
  124. 124.
    Chen C-Y, Chi Y-H, Mutalif RA, Starost MF, Myers TG, Anderson SA, Stewart CL, Jeang K-T. Accumulation of the inner nuclear envelope protein Sun1 is pathogenic in progeric and dystrophic laminopathies. Cell. 2012;149:565–77. Scholar
  125. 125.
    Choi JC, Worman HJ. Reactivation of autophagy ameliorates LMNA cardiomyopathy. Autophagy. 2013;9:110–1. Scholar
  126. 126.
    Choi JC, Muchir A, Wu W, Iwata S, Homma S, Morrow JP, Worman HJ. Temsirolimus activates autophagy and ameliorates cardiomyopathy caused by lamin A/C gene mutation. Sci Transl Med. 2012;4:144ra102. Scholar
  127. 127.
    Lenain C, Gusyatiner O, Douma S, van den Broek B, Peeper DS. Autophagy-mediated degradation of nuclear envelope proteins during oncogene-induced senescence. Carcinogenesis. 2015;36:1263–74. Scholar
  128. 128.
    Dou Z, Xu C, Donahue G, Shimi T, Pan J-A, Zhu J, Ivanov A, Capell BC, Drake AM, Shah PP, Catanzaro JM, Ricketts MD, Lamark T, Adam SA, Marmorstein R, Zong W-X, Johansen T, Goldman RD, Adams PD, Berger SL. Autophagy mediates degradation of nuclear lamina. Nature. 2015;527:105–9. Scholar
  129. 129.
    Song X, Narzt MS, Nagelreiter IM, Hohensinner P, Terlecki-Zaniewicz L, Tschachler E, Grillari J, Gruber F. Autophagy deficient keratinocytes display increased DNA damage, senescence and aberrant lipid composition after oxidative stress in vitro and in vivo. Redox Biol. 2017;11:219–30. Scholar
  130. 130.
    Akinduro O, Sully K, Patel A, Robinson DJ, Chikh A, McPhail G, Braun KM, Philpott MP, Harwood CA, Byrne C, O'Shaughnessy RFL, Bergamaschi D. Constitutive autophagy and Nucleophagy during epidermal differentiation. J Invest Dermatol. 2016;136:1460–70. Scholar
  131. 131.
    Musich PR, Zou Y. DNA-damage accumulation and replicative arrest in Hutchinson-Gilford progeria syndrome. Biochem Soc Trans. 2011;39:1764–9. Scholar
  132. 132.
    Sotiropoulou PA, Blanpain C. Development and homeostasis of the skin epidermis. Cold Spring Harb Perspect Biol. 2012;4:a008383. Scholar
  133. 133.
    Goldstein J, Horsley V. Home sweet home: skin stem cell niches. CMLS, Cell Mol Life Sci. 2012;69:2573–82. Scholar
  134. 134.
    Sotiropoulou PA, Candi A, Mascré G, De Clercq S, Youssef KK, Lapouge G, Dahl E, Semeraro C, Denecker G, Marine J-C, Blanpain C. Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. Nat Cell Biol. 2010;12:572–82. Scholar
  135. 135.
    Huang X, Pan Y, Cao D, Fang S, Huang K, Chen J, Chen A. UVA-induced upregulation of progerin suppresses 53BP1-mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation. Oncol Rep. 2017;37:3617–24. Scholar
  136. 136.
    Sotiropoulou PA, Karambelas AE, Debaugnies M, Candi A, Bouwman P, Moers V, Revenco T, Rocha AS, Sekiguchi K, Jonkers J, Blanpain C. BRCA1 deficiency in skin epidermis leads to selective loss of hair follicle stem cells and their progeny. Genes Dev. 2013;27:39–51. Scholar
  137. 137.
    Vogel V. Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu Rev Biophys Biomol Struct. 2006;35:459–88. Scholar
  138. 138.
    Ivanovska IL, Shin J-W, Swift J, Discher DE. Stem cell mechanobiology: diverse lessons from bone marrow. Trends Cell Biol. 2015;25:523–32. Scholar
  139. 139.
    Jain N, Iyer KV, Kumar A, Shivashankar GV. Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility. Proc Natl Acad Sci USA. 2013;110:11349–54. Scholar
  140. 140.
    Ramdas NM, Shivashankar GV. Cytoskeletal control of nuclear morphology and chromatin organization. J Mol Biol. 2015;427:695–706. Scholar
  141. 141.
    Versaevel M, Braquenier J-B, Riaz M, Grevesse T, Lantoine J, Gabriele S. Super-resolution microscopy reveals LINC complex recruitment at nuclear indentation sites. Sci Rep. 2014;4:7362. Scholar
  142. 142.
    Alam SG, Zhang Q, Prasad N, Li Y, Chamala S, Kuchibhotla R, Kc B, Aggarwal V, Shrestha S, Jones AL, Levy SE, Roux KJ, Nickerson JA, Lele TP. The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity. Sci Rep. 2016;6:38063. Scholar
  143. 143.
    McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004;6:483–95. Scholar
  144. 144.
    Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126:677–89. Scholar
  145. 145.
    le Duc Q, Shi Q, Blonk I, Sonnenberg A, Wang N, Leckband D, de Rooij J. Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J Cell Biol. 2010;189:1107–15. Scholar
  146. 146.
    Yonemura S, Wada Y, Watanabe T, Nagafuchi A, Shibata M. Alpha-catenin as a tension transducer that induces adherens junction development. Nat Cell Biol. 2010;12:533–42. Scholar
  147. 147.
    Galbraith CG, Yamada KM, Sheetz MP. The relationship between force and focal complex development. J Cell Biol. 2002;159:695–705. Scholar
  148. 148.
    Deguchi S, Maeda K, Ohashi T, Sato M. Flow-induced hardening of endothelial nucleus as an intracellular stress-bearing organelle. J Biomech. 2005;38:1751–9. Scholar
  149. 149.
    Philip JT, Dahl KN. Nuclear mechanotransduction: response of the lamina to extracellular stress with implications in aging. J Biomech. 2008;41:3164–70. Scholar
  150. 150.
    Le HQ, Ghatak S, Yeung C-YC, Tellkamp F, Günschmann C, Dieterich C, Yeroslaviz A, Habermann B, Pombo A, Niessen CM, Wickström SA. Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nat Cell Biol. 2016;18:864–75. Scholar
  151. 151.
    Morris GE, Randles KN. Nesprin isoforms: are they inside or outside the nucleus? Biochem Soc Trans. 2010;38:278–80. Scholar
  152. 152.
    Wheeler MA, Davies JD, Zhang Q, Emerson LJ, Hunt J, Shanahan CM, Ellis JA. Distinct functional domains in nesprin-1alpha and nesprin-2beta bind directly to emerin and both interactions are disrupted in X-linked Emery-Dreifuss muscular dystrophy. Exp Cell Res. 2007;313:2845–57. Scholar
  153. 153.
    Mislow JMK, Holaska JM, Kim MS, Lee KK, Segura-Totten M, Wilson KL, McNally EM. Nesprin-1alpha self-associates and binds directly to emerin and lamin A in vitro. FEBS Lett. 2002;525:135–40.CrossRefPubMedGoogle Scholar
  154. 154.
    Haque F, Lloyd DJ, Smallwood DT, Dent CL, Shanahan CM, Fry AM, Trembath RC, Shackleton S. SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton. Mol Cell Biol. 2006;26:3738–51. Scholar
  155. 155.
    Bengtsson L, Otto H. LUMA interacts with emerin and influences its distribution at the inner nuclear membrane. J Cell Sci. 2008;121:536–48. Scholar
  156. 156.
    Heald R, McKeon F. Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis. Cell. 1990;61:579–89.CrossRefPubMedGoogle Scholar
  157. 157.
    Khatau SB, Kim D-H, Hale CM, Bloom RJ, Wirtz D. The perinuclear actin cap in health and disease. Nucleus. 2010;1:337–42. Scholar
  158. 158.
    Kim D-H, Wirtz D. Cytoskeletal tension induces the polarized architecture of the nucleus. Biomaterials. 2015;48:161–72. Scholar
  159. 159.
    Tajik A, Zhang Y, Wei F, Sun J, Jia Q, Zhou W, Singh R, Khanna N, Belmont AS, Wang N. Transcription upregulation via force-induced direct stretching of chromatin. Nat Mater. 2016;15:1287–96. Scholar
  160. 160.
    Autore F, Pfuhl M, Quan X, Williams A, Roberts RG, Shanahan CM, Fraternali F. Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins. PLoS One. 2013;8:e63633. Scholar
  161. 161.
    Johnson CP, Tang H-Y, Carag C, Speicher DW, Discher DE. Forced unfolding of proteins within cells. Science. 2007;317:663–6. Scholar
  162. 162.
    Fillingham I, Gingras AR, Papagrigoriou E, Patel B, Emsley J, Critchley DR, Roberts GCK, Barsukov IL. A vinculin binding domain from the talin rod unfolds to form a complex with the vinculin head. Structure. 2005;13:65–74. Scholar
  163. 163.
    Lu W, Schneider M, Neumann S, Jaeger V-M, Taranum S, Munck M, Cartwright S, Richardson C, Carthew J, Noh K, Goldberg M, Noegel AA, Karakesisoglou I. Nesprin interchain associations control nuclear size. CMLS, Cell Mol Life Sci. 2012;69:3493–509. Scholar
  164. 164.
    Balikov DA, Brady SK, Ko UH, Shin JH, de Pereda JM, Sonnenberg A, Sung H-J, Lang MJ. The nesprin-cytoskeleton interface probed directly on single nuclei is a mechanically rich system. Nucleus. 2017;5:1–14. Scholar
  165. 165.
    Uzer G, Thompson WR, Sen B, Xie Z, Yen SS, Miller S, Bas G, Styner M, Rubin CT, Judex S, Burridge K, Rubin J. Cell Mechanosensitivity to extremely low-magnitude signals is enabled by a LINCed nucleus. Stem Cells. 2015;33:2063–76. Scholar
  166. 166.
    Tambe DT, Hardin CC, Angelini TE, Rajendran K, Park CY, Serra-Picamal X, Zhou EH, Zaman MH, Butler JP, Weitz DA, Fredberg JJ, Trepat X. Collective cell guidance by cooperative intercellular forces. Nat Mater. 2011;10:469–75. Scholar
  167. 167.
    Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179–83. Scholar
  168. 168.
    Zhang H, Pasolli HA, Fuchs E. Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proc Natl Acad Sci USA. 2011;108:2270–5. Scholar
  169. 169.
    Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, Kreger BT, Vasioukhin V, Avruch J, Brummelkamp TR, Camargo FD. Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell. 2011;144:782–95. Scholar
  170. 170.
    Silvis MR, Kreger BT, Lien W-H, Klezovitch O, Rudakova GM, Camargo FD, Lantz DM, Seykora JT, Vasioukhin V. α-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the transcriptional coactivator Yap1. Sci Signal. 2011;4:ra33. Scholar
  171. 171.
    Luxenburg C, Pasolli HA, Williams SE, Fuchs E. Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation. Nat Cell Biol. 2011;13:203–14. Scholar
  172. 172.
    Koegel H, Tobel von L, Schäfer M, Alberti S, Kremmer E, Mauch C, Hohl D, Wang X-J, Beer H-D, Bloch W, Nordheim A, Werner S. Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice. J Clin Invest. 2009;119:899–910. Scholar
  173. 173.
    Connelly JT, Gautrot JE, Trappmann B, Tan DW-M, Donati G, Huck WTS, Watt FM. Actin and serum response factor transduce physical cues from the microenvironment to regulate epidermal stem cell fate decisions. Nat Cell Biol. 2010;12:711–8. Scholar
  174. 174.
    Lin C, Hindes A, Burns CJ, Koppel AC, Kiss A, Yin Y, Ma L, Blumenberg M, Khnykin D, Jahnsen FL, Crosby SD, Ramanan N, Efimova T. Serum response factor controls transcriptional network regulating epidermal function and hair follicle morphogenesis. J Invest Dermatol. 2013;133:608–17. Scholar
  175. 175.
    Lammerding J, Schulze PC, Takahashi T, Kozlov S, Sullivan T, Kamm RD, Stewart CL, Lee RT. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest. 2004;113:370–8. Scholar
  176. 176.
    Lammerding J, Hsiao J, Schulze PC, Kozlov S, Stewart CL, Lee RT. Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J Cell Biol. 2005;170:781–91. Scholar
  177. 177.
    Ho CY, Jaalouk DE, Vartiainen MK, Lammerding J. Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics. Nature. 2013;497:507–11. Scholar
  178. 178.
    Bertrand AT, Ziaei S, Ehret C, Duchemin H, Mamchaoui K, Bigot A, Mayer M, Quijano-Roy S, Desguerre I, Lainé J, Ben Yaou R, Bonne G, Coirault C. Cellular microenvironments reveal defective mechanosensing responses and elevated YAP signaling in LMNA-mutated muscle precursors. J Cell Sci. 2014;127:2873–84. Scholar
  179. 179.
    Willer MK, Carroll CW. Substrate stiffness-dependent regulation of the SRF-Mkl1 co-activator complex requires the inner nuclear membrane protein Emerin. J Cell Sci. 2017;130:2111–8. Scholar
  180. 180.
    Zanconato F, Forcato M, Battilana G, Azzolin L, Quaranta E, Bodega B, Rosato A, Bicciato S, Cordenonsi M, Piccolo S. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth. Nat Cell Biol. 2015;17:1218–27. Scholar
  181. 181.
    Holaska JM, Kowalski AK, Wilson KL. Emerin caps the pointed end of actin filaments: evidence for an actin cortical network at the nuclear inner membrane. PLoS Biol. 2004;2:E231. Scholar
  182. 182.
    Schreiber KH, Kennedy BK. When lamins go bad: nuclear structure and disease. Cell. 2013;152:1365–75. Scholar
  183. 183.
    McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, Collins FS, Dekker J, Cao K. Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res. 2013;23:260–9. Scholar
  184. 184.
    Gonzalo S, Kreienkamp R. DNA repair defects and genome instability in Hutchinson-Gilford progeria syndrome. Curr Opin Cell Biol. 2015;34:75–83. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Cell BiologyYale School of MedicineNew HavenUSA
  2. 2.Department of DermatologyYale School of MedicineNew HavenUSA
  3. 3.Department of Molecular, Cell and Developmental BiologyYale UniversityNew HavenUSA

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