The NuRD Complex: Linking Histone Modification to Nucleosome Remodeling

Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 274)


ATP-dependent nucleosome remodeling and core histone tail modifications play important roles in chromatin function. Purification and characterization of the NuRD/Mi-2 complex, which possesses both nucleosome remodeling and histone deacetylase activities, suggests that ATP-dependent nucleosome remodeling and histone tail modification can be coupled. Recent studies indicate that NuRD is an integral part of the MeCPl complex, suggesting that nucleosome remodeling and histone deacetylation play important roles in methylated DNA silencing. Studies in Caenorhabditis elegans have revealed important functions of the NuRD complex in embryonic patterning and Ras signaling. Accumulating evidence indicates that NuRD may regulate transcription of specific genes by interacting with specific transcriptional factors. In addition, it may also participate in genome-wide transcriptional regulation through an association with histone tails.


Histone Deacetylase Histone Deacetylation Histone Tail Nucleosome Remodel Embryonic Patterning 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Ahringer J (2000) NuRD and SIN3 histone deacetylase complexes in development. Trends Genet 16:351–6PubMedCrossRefGoogle Scholar
  2. Bird A (2002) DNAmethylation patterns and epigenetic memory. Genes Dev 16:6–21PubMedCrossRefGoogle Scholar
  3. Bird AP, Wolffe AP (1999) Methylation-induced repression-belts, braces, and chromatin. Cell 99:451–4PubMedCrossRefGoogle Scholar
  4. Boyer LA, Logie C, Bonte E, Becker PB, Wade PA, Wolffe AP, Wu C, Imbalzano AN, Peterson CL (2000) Functional delineation of three groups of the ATP-dependent family of chromatin remodeling enzymes. J Biol Chem 275:18864–70PubMedCrossRefGoogle Scholar
  5. Brehm A, Langst G, Kehle J, Clapier CR, Imhof A, Eberharter A, Muller J, Becker PB (2000) dMi-2 and ISWI chromatin remodelling factors have distinct nucleosome binding and mobilization properties. EMBOJ 19:4332–41CrossRefGoogle Scholar
  6. Brehm A, Nielsen SJ, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T (1999) The E7oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBOJ 18:2449–58CrossRefGoogle Scholar
  7. Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY, Allis CD (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84:843–51PubMedCrossRefGoogle Scholar
  8. Ch’ng Q, Kenyon C (1999) egl-27 generates anteroposterior patterns of cell fusion in C. elegans by regulating Hox gene expression and Hox protein function. Development 126:3303–12Google Scholar
  9. Chen Z, Han M (2001) Role of C. elegans lin-40 MTAin vulval fate specification and morphogenesis. Development 128:4911–21PubMedGoogle Scholar
  10. Cote J, Quinn J, Workman JL, Peterson CL (1994) Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science 265:53–60PubMedCrossRefGoogle Scholar
  11. Cress WD, Seto E (2000) Histone deacetylases, transcriptional control, and cancer. J Cell Physiol 184:1–16PubMedCrossRefGoogle Scholar
  12. Esteller M, Herman JG (2002) Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol 196:1–7PubMedCrossRefGoogle Scholar
  13. Feng Q, Cao R, Kia L, Erdjument-Bromage H, Tempst P, Zhang Y (2002) Identification and functional characterization of the p66/p68 components of the MeCPl complex. Mol Cell Biol 22:536–46PubMedCrossRefGoogle Scholar
  14. Feng Q, Zhang Y (2001) The MeCPl complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes. Genes Dev 15:827–32PubMedGoogle Scholar
  15. Ferguson EL, Horvitz HR (1989) The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways. Genetics 123:109–21PubMedGoogle Scholar
  16. Guenther MG, Barak O, Lazar MA (2001) The SMRTand N-CoR corepressors are activating cofactors for histone deacetylase 3. Mol Cell Biol 21:6091–101PubMedCrossRefGoogle Scholar
  17. Guschin D, Wade PA, Kikyo N, Wolffe AP (2000) ATP-Dependent histone octamer mobilization and histone deacetylation mediated by the Mi-2 chromatin remodeling complex. Biochemistry 39:5238–45PubMedCrossRefGoogle Scholar
  18. Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL (1998) A role for histone deacetylase activity in HDACI-mediated transcriptional repression. Proc Natl Acad Sci USA 95:3519–24PubMedCrossRefGoogle Scholar
  19. Hebbes TR, Thorne AW, Crane-Robinson C (1988) A direct link between core histone acetylation and transcriptionally active chromatin. EMBOJ 7:1395–402Google Scholar
  20. Hendrich B, Bird A (1998) Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18:6538–47PubMedGoogle Scholar
  21. Hendrich B, Bird A (2000) Mammalian methyltransferases and methyl-CpG-binding domains: proteins involved in DNAmethylation. Curr Top Microbiol Immunol 249:55–74PubMedCrossRefGoogle Scholar
  22. Hendrich B, Guy J, Ramsahoye B, Wilson VA, Bird A (2001) Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev 15:710–23PubMedCrossRefGoogle Scholar
  23. Herman JG, Baylin SB (2000) Promoter-region hypermethylation and gene silencing in human cancer. Curr Top Microbiol ImmunoI 249:35–54CrossRefGoogle Scholar
  24. Herman MA, Ch’ng Q, Hettenbach SM, Ratliff TM, Kenyon C, Herman RK (1999) EGL-27 is similar to a metastasis-associated factor and controls cell polarity and cell migration in C. elegans. Development 126:1055–64PubMedGoogle Scholar
  25. Iguchi H, Imura G, Toh Y, Ogata Y (2000) Expression of MTAl, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer. Int J Oncol 16:1211–4PubMedGoogle Scholar
  26. Jones PA (1999) The DNAmethylation paradox. Trends Genet 15:34–7PubMedCrossRefGoogle Scholar
  27. Kadosh D, Struhl K (1998) Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo. Genes Dev 12:797–805PubMedCrossRefGoogle Scholar
  28. Kehle J, Beuchle D, Treuheit S, Christen B, Kennison JA, Bienz M, Muller J (1998) dMi-2, a hunchback-interacting protein that functions in polycomb repression. Science 282:1897–900PubMedCrossRefGoogle Scholar
  29. Kim J, Sif S, Jones B, Jackson A, Koipally J, Heller E, Winandy S, Viel A, Sawyer A, Ikeda T, Kingston R, Georgopoulos K (1999) Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity 10:345–55PubMedCrossRefGoogle Scholar
  30. Kingston RE, Narlikar GJ (1999) ATP-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev 13:2339–52PubMedCrossRefGoogle Scholar
  31. Knoepfler PS, Eisenman RN (1999) Sin meets NuRD and other tails of repression. Cell 99:447–50PubMedCrossRefGoogle Scholar
  32. Kornberg RD, Lorch Y (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98:285–94PubMedCrossRefGoogle Scholar
  33. Kuo MH, Zhou J, Jambeck P, Churchill ME, Allis CD (1998) Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo. Genes Dev 12:627–39PubMedCrossRefGoogle Scholar
  34. Kwon H, Imbalzano AN, Khavari PA, Kingston RE, Green MR (1994) Nucleosome disruption and enhancement of activator binding by a human SWl/SNF complex. Nature 370:477–81PubMedCrossRefGoogle Scholar
  35. Lu X, Horvitz HR (1998) lin-35 and lin-53, two genes that antagonize a C. elegans Ras pathway, encode proteins similar to Rb and its binding protein RbAp48. Cell 95:981–91PubMedCrossRefGoogle Scholar
  36. Luo J, Su F, Chen D, Shiloh A, Gu W (2000) Deacetylation of pS3 modulates its effect on cell growth and apoptosis. Nature 408:377–81PubMedCrossRefGoogle Scholar
  37. Martinez-Balbas MA, Tsukiyama T, Gdula D, Wu C (1998) Drosophila NURF-55, a WD repeat protein involved in histone metabolism. Proc Natl Acad Sci USA 95:132–7PubMedCrossRefGoogle Scholar
  38. Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R (2001) Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol 3:30–7PubMedCrossRefGoogle Scholar
  39. Murawsky CM, Brehm A, Badenhorst P, Lowe N, Becker PB, Travers AA (2001) Tramtrack69 interacts with the dMi-2 subunit of the Drosophila NuRD chromatin remodelling complex. EMBORep 2:1089–94CrossRefGoogle Scholar
  40. Nan X, Meehan RR, Bird A (1993) Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res 21:4886–92PubMedCrossRefGoogle Scholar
  41. Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (1999) MBD2is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet 23:58–61PubMedGoogle Scholar
  42. Nishioka K, Chuikov S, Sarma K, Erdjument-Bromage H, Allis CD, Tempst P, Reinberg D (2002) Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev 16:479–89PubMedCrossRefGoogle Scholar
  43. Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M (2001) Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA.Cell 105:487–97PubMedCrossRefGoogle Scholar
  44. Parthun MR, Widom J, Gottschling DE (1996) The major cytoplasmic histone acetyltransferase in yeast: links to chromatin replication and histone metabolism. Cell 87:85–94PubMedCrossRefGoogle Scholar
  45. Pazin MJ, Kadonaga JT (1997) SWI2/SNF2 and related proteins: ATP-driven motors that disrupt protein-DNA interactions? Cell 88:737–40PubMedCrossRefGoogle Scholar
  46. Qian YW, Lee EY (1995) Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast. J Biol Chem 270:25507–13PubMedCrossRefGoogle Scholar
  47. Qian YW, Wang YC, Hollingsworth RE Jr, Jones D, Ling N, Lee EY (1993) A retinoblastoma-binding protein related to a negative regulator of Ras in yeast. Nature 364:648–52PubMedCrossRefGoogle Scholar
  48. Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Annu Rev Biochem 70:81–120PubMedCrossRefGoogle Scholar
  49. Ruggieri R, Tanaka K, Nakafuku M, Kaziro Y, Toh-e A, Matsumoto K (1989) MSI1, a negative regulator of the RAS-cAMP pathway in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 86:8778–82PubMedCrossRefGoogle Scholar
  50. Sasaki H, Moriyama S, Nakashima Y, Kobayashi Y, Yukiue H, Kaji M, Fukai I, Kiriyama M, Yamakawa Y, Fujii Y (2002) Expression of the MTA! mRNA in advanced lung cancer. Lung Cancer 35:149–54PubMedCrossRefGoogle Scholar
  51. Schultz DC, Friedman JR, Rauscher FJ, 3rd (2001) Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-l form a cooperative unit that recruits a novel isoform of the Mi-2alpha subunit of NuRD. Genes Dev 15:428–43PubMedCrossRefGoogle Scholar
  52. Seelig HP, Moosbrugger I, Ehrfeld H, Fink T, Renz M, Genth E (1995) The major dermatomyositis-specific Mi-2 auto antigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum 38:1389–99PubMedCrossRefGoogle Scholar
  53. Seelig HP, Renz M, Targoff IN, Ge Q, Frank MB (1996) Two forms of the major antigenic protein of the dermatomyositis-specific Mi-2 autoantigen. Arthritis Rheum 39:1769–71PubMedCrossRefGoogle Scholar
  54. Shi Y, Mello C (1998) A CBP/p300 homolog specifies multiple differentiation pathways in Caenorhabditis elegans. Genes Dev 12:943–55PubMedCrossRefGoogle Scholar
  55. Solari F, Ahringer J (2000) NURD-complex genes antagonise Ras-induced vulval development in Caenorhabditis elegans. Curr Biol 10:223–6PubMedCrossRefGoogle Scholar
  56. Solari F, Bateman A, Ahringer J (1999) The Caenorhabditis elegans genes egl-27 and egr-l are similar to MTA1, a member of a chromatin regulatory complex, and are redundantly required for embryonic patterning. Development 126:2483–94PubMedGoogle Scholar
  57. Sternberg PW, Han M (1998) Genetics of RASsignaling in C. elegans. Trends Genet 14:466–72PubMedCrossRefGoogle Scholar
  58. Tatematsu KI, Yamazaki T, Ishikawa F (2000) MBD2-MBD3complex binds to hernimethylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells 5:677–88PubMedCrossRefGoogle Scholar
  59. Taunton J, Hassig CA, Schreiber SL (1996) Amammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272:408–11PubMedCrossRefGoogle Scholar
  60. Toh Y, Kuwano H, Mori M, Nicolson GL, Sugimachi K (1999) Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer 79:1723–6PubMedCrossRefGoogle Scholar
  61. Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y, Nicolson GL, Sugimachi K (1997) Overexpression of the MTAI gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer 74:459–63PubMedCrossRefGoogle Scholar
  62. Toh Y, Pencil SD, Nicolson GL (1994) A novel candidate metastasis-associated gene, mtal, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses. J Biol Chem 269:22958–63PubMedGoogle Scholar
  63. Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (1998) Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature 395:917–21PubMedCrossRefGoogle Scholar
  64. Tyler JK, Bulger M, Kamakaka RT, Kobayashi R, Kadonaga JT (1996) The p55 subunit of Drosophila chromatin assembly factor 1 is homologous to a histone deacetylase-associated protein. Mol Cell Biol 16:6149–59PubMedGoogle Scholar
  65. Verreault A, Kaufman PD, Kobayashi R, Stillman B (1998) Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase. Curr Biol 8:96–108PubMedCrossRefGoogle Scholar
  66. Verreault A, Kaufman PD, Kobayashi R, Stillman B (1996) Nucleosome assembly by a complex of CAF-1 and acetylated histones H3/H4. Cell 87:95–104PubMedCrossRefGoogle Scholar
  67. Vidal M, Gaber RF (1991) RPD3 encodes a second factor required to achieve maximum positive and negative transcriptional states in Saccharomyces cerevisiae. Mol Cell Biol 11:6317–27PubMedGoogle Scholar
  68. Vignali M, Hassan AH, Neely KE, Workman JL (2000) ATP-dependent chromatinremodeling complexes. Mol Cell Biol 20:1899–910PubMedCrossRefGoogle Scholar
  69. Van Holde KE (1988) Histone modifications. In Chromatin,Springerseries in molecular biology (ed. A. Rich), pp.111–148. Springer, NewYorkGoogle Scholar
  70. Von Zelewsky T, Palladino F, Brunschwig K, Tobler H, Hajnal A, Muller F (2000) The C. elegans Mi-2 chromatin-remodelling proteins function in vulval cell fate determination. Development 127:5277–84Google Scholar
  71. Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP (1999) Mi-2 complex couples DNAmethylation to chromatin remodelling and histone deacetylation. Nat Genet 23:62–6PubMedGoogle Scholar
  72. Wade PA, Jones PL, Vermaak D, Wolffe AP (1998) A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Curr Biol 8:843–6PubMedCrossRefGoogle Scholar
  73. Wang HB, Zhang Y (2001) Mi2, an auto-antigen for dermatomyositis, is an ATPdependent nucleosome remodeling factor. Nucleic Acids Res 29:2517–21PubMedCrossRefGoogle Scholar
  74. Wang L, Liu L, Berger SL (1998) Critical residues for histone acetylation by GenS, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo. Genes Dev 12:640–53PubMedCrossRefGoogle Scholar
  75. Wolffe AP (2000) Transcriptional control: imprinting insulation. Curr Biol 10:R463–5PubMedCrossRefGoogle Scholar
  76. Woodage T, Basrai MA, Baxevanis AD, Hieter P, Collins FS (1997) Characterization of the CHD family of proteins. Proc Natl Acad Sci USA 94:11472–7PubMedCrossRefGoogle Scholar
  77. Wu J, Grunstein M (2000) 25 years after the nucleosome model: chromatin modifications. Trends Biochem Sci 25:619–23PubMedCrossRefGoogle Scholar
  78. Xia L, Zhang Y (2001) Sp1 and ETS family transcription factors regulate the mouse Mta2 gene expression. Gene 268:77–85PubMedCrossRefGoogle Scholar
  79. Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W (1998) NURD,a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell 2:851–61PubMedCrossRefGoogle Scholar
  80. Yang WM, Inouye C, Zeng Y, Bearss D, Seta E (1996) Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Proc Natl Acad Sci USA 93:12845–50PubMedCrossRefGoogle Scholar
  81. Zegerman P, Canas B, Pappin D, Kouzarides T (2002) Histone H3lysine 4 methylation disrupts the binding of the nucleosome remodelling and deacetylase (NuRD) repressor complex. J Biol Chem 15:15Google Scholar
  82. Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D (1997) Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex. Cell 89:357–64PubMedCrossRefGoogle Scholar
  83. Zhang Y, Leroy G, Seelig HP, Lane WS, Reinberg D (1998) The dermatomyositisspecific auto antigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95:79–89CrossRefGoogle Scholar
  84. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNAmethylation. Genes Dev 13:1924–35PubMedCrossRefGoogle Scholar
  85. Zhang Y, Reinberg D (2001) Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev 15:2343–60PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  1. 1.Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel HillUSA

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