Skip to main content
SpringerLink
Log in

Epigenetic Regulations in Cardiac Development

  • Chapter
  • First Online:
Epigenetics in Cardiac Disease

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 1))

  • 833 Accesses

Abstract

Abnormalities in heart development lead to congenital heart disease affecting ~1 % of newborns. Severe congenital heart disease can cause heart dysfunction at very early development stages, whereas mild heart defects may trigger heart dysfunction until adulthood. The adult mammalian heart has very limited regenerative capacity. Designing therapeutic strategies for congenital heart disease is likely dependent on understanding the mechanisms of heart development. Heart development is orchestrated by complicated biological processes, including signal transduction, transcriptional regulation, and epigenetic regulation. In this chapter, we review the current processes of epigenetic modifications during heart development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Agger K, Cloos PA, Christensen J, Pasini D, Rose S, Rappsilber J, Issaeva I, Canaani E, Salcini AE, Helin K (2007) UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449:731–734

    CAS  PubMed  Google Scholar 

  • Alby C, Bessieres B, Bieth E, Attie-Bitach T, Fermont L, Citony I, Razavi F, Vekemans M, Escande F, Manouvrier S et al (2013) Contiguous gene deletion of TBX5 and TBX3 leads to a varible phenotype with combined features of Holt-Oram and ulnar-mammary syndromes. Am J Med Genet A 161A:1797–1802

    PubMed  Google Scholar 

  • Arnold MA, Kim Y, Czubryt MP, Phan D, McAnally J, Qi X, Shelton JM, Richardson JA, Bassel-Duby R, Olson EN (2007) MEF2C transcription factor controls chondrocyte hypertrophy and bone development. Dev Cell 12:377–389

    CAS  PubMed  Google Scholar 

  • Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395

    CAS  PubMed  Google Scholar 

  • Biben C, Harvey RP (1997) Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development. Genes Dev 11:1357–1369

    CAS  PubMed  Google Scholar 

  • Bodmer R (1993) The gene tinman is required for specification of the heart and visceral muscles in Drosophila. Development 118:719–729

    CAS  PubMed  Google Scholar 

  • Bondue A, Lapouge G, Paulissen C, Semeraro C, Iacovino M, Kyba M, Blanpain C (2008) Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. Cell Stem Cell 3:69–84

    CAS  PubMed  Google Scholar 

  • Bondue A, Blanpain C (2010) Mesp1: a key regulator of cardiovascular lineage commitment. Circ Res 107:1414–1427

    CAS  PubMed  Google Scholar 

  • Brown DD, Martz SN, Binder O, Goetz SC, Price BM, Smith JC, Conlon FL (2005) Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis. Development 132:553–563

    CAS  PubMed  Google Scholar 

  • Bruneau BG, Nemer G, Schmitt JP, Charron F, Robitaille L, Caron S, Conner DA, Gessler M, Nemer M, Seidman CE et al (2001) A murine model of Holt-Oram syndrome defines roles of the T-box transcription factor Tbx5 in cardiogenesis and disease. Cell 106:709–721

    CAS  PubMed  Google Scholar 

  • Bultman S, Gebuhr T, Yee D, La Mantia C, Nicholson J, Gilliam A, Randazzo F, Metzger D, Chambon P, Crabtree G et al (2000) A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. Mol Cell 6:1287–1295

    CAS  PubMed  Google Scholar 

  • Burgold T, Voituron N, Caganova M, Tripathi PP, Menuet C, Tusi BK, Spreafico F, BĂ©vengut M, Gestreau C, Buontempo S et al (2012) The H3K27 demethylase JMJD3 is required for maintenance of the embryonic respiratory neuronal network, neonatal breathing, and survival. Cell Rep 2:1244–1258

    CAS  PubMed  Google Scholar 

  • Chakraborty S, Yutzey KE (2012) Tbx20 regulation of cardiac cell proliferation and lineage specialization during embryonic and fetal development in vivo. Dev Biol 363:234–246

    CAS  PubMed  Google Scholar 

  • Christophorou MA, Castelo-Branco G, Halley-Stott RP, Oliveira CS, Loos R, Radzisheuskaya A, Mowen KA, Bertone P, Silva JC, Zernicka-Goetz M et al (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507:104–108

    CAS  PubMed  Google Scholar 

  • Charron F, Paradis P, Bronchain O, Nemer G, Nemer M (1999) Cooperative interaction between GATA-4 and GATA-6 regulates myocardial gene expression. Mol Cell Biol 19:4355–4365

    CAS  PubMed  Google Scholar 

  • Chen JN, Fishman MC (1996) Zebrafish tinman homolog demarcates the heart field and initiates myocardial differentiation. Development 122:3809–3816

    CAS  PubMed  Google Scholar 

  • Christensen J, Agger K, Cloos PA, Pasini D, Rose S, Sennels L, Rappsilber J, Hansen KH, Salcini AE, Helin K (2007) RBP2 belongs to a family of demethylases, specific for tri-and dimethylated lysine 4 on histone 3. Cell 128:1063–1076

    CAS  PubMed  Google Scholar 

  • Christoffels VM, Mommersteeg MT, Trowe MO, Prall OW, de Gier-de Vries C, Soufan AT, Bussen M, Schuster-Gossler K, Harvey RP, Moorman AF et al (2006) Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18. Circ Res 98:1555–1563

    CAS  PubMed  Google Scholar 

  • Clapier CR, Cairns BR (2009) The biology of chromatin remodeling complexes. Annu Rev Biochem 78:273–304

    CAS  PubMed  Google Scholar 

  • Cleaver OB, Patterson KD, Krieg PA (1996) Overexpression of the tinman-related genes XNkx-2.5 and XNkx-2.3 in Xenopus embryos results in myocardial hyperplasia. Development 122:3549–3556

    CAS  PubMed  Google Scholar 

  • Cserjesi P, Brown D, Lyons GE, Olson EN (1995) Expression of the novel basic helix-loop-helix gene eHAND in neural crest derivatives and extraembryonic membranes during mouse development. Dev Biol 170:664–678

    CAS  PubMed  Google Scholar 

  • Dawlaty MM, Breiling A, Le T, Barrasa MI, Raddatz G, Gao Q, Powell BE, Cheng AW, Faull KF, Lyko F et al (2014) Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev Cell 29:102–111

    CAS  PubMed  Google Scholar 

  • Dodou E, Verzi MP, Anderson JP, Xu SM, Black BL (2004) Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development. Development 131:3931–3942

    CAS  PubMed  Google Scholar 

  • Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 10:2709–2721

    CAS  PubMed  Google Scholar 

  • Flavell SW, Cowan CW, Kim TK, Greer PL, Lin Y, Paradis S, Griffith EC, Hu LS, Chen C, Greenberg ME (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311:1008–1012

    CAS  PubMed  Google Scholar 

  • Fodor BD, Kubicek S, Yonezawa M, O’Sullivan RJ, Sengupta R, Perez-Burgos L, Opravil S, Mechtler K, Schotta G, Jenuwein T (2006) Jmjd2b antagonizes H3K9 trimethylation at pericentric heterochromatin in mammalian cells. Genes Dev 20:1557–1562

    CAS  PubMed  Google Scholar 

  • Gajewski K, Kim Y, Choi CY, Schulz RA (1998) Combinatorial control of Drosophila mef2 gene expression in cardiac and somatic muscle cell lineages. Dev Genes Evol 208:382–392

    CAS  PubMed  Google Scholar 

  • Garcia-Martinez V, Schoenwolf GC (1993) Primitive-streak origin of the cardiovascular system in avian embryos. Dev Biol 159:706–719

    CAS  PubMed  Google Scholar 

  • Garry DJ, Olson EN (2006) A common progenitor at the heart of development. Cell 127:1101–1104

    CAS  PubMed  Google Scholar 

  • Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K et al (2003) GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 424:443–447

    CAS  PubMed  Google Scholar 

  • Ghosh TK, Packham EA, Bonser AJ, Robinson TE, Cross SJ, Brook JD (2001) Characterization of the TBX5 binding site and analysis of mutations that cause Holt-Oram syndrome. Hum Mol Genet 10:1983–1994

    CAS  PubMed  Google Scholar 

  • Glaser S, Schaft J, Lubitz S, Vintersten K, van der Hoeven F, Tufteland KR, Aasland R, Anastassiadis K, Ang SL, Stewart AF (2006) Multiple epigenetic maintenance factors implicated by the loss of Mll2 in mouse development. Development 133:1423–1432

    CAS  PubMed  Google Scholar 

  • Goll MG, Bestor TH (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74:481–514

    CAS  PubMed  Google Scholar 

  • Granados-Riveron JT, Ghosh TK, Pope M, Bu’Lock F, Thornborough C, Eason J, Kirk EP, Fatkin D, Feneley MP, Harvey RP et al (2010) Alpha-cardiac myosin heavy chain (MYH6) mutations affecting myofibril formation are associated with congenital heart defects. Hum Mol Genet 19:4007–4016

    CAS  PubMed  Google Scholar 

  • Green MR (2005) Eukaryotic transcription activation: right on target. Mol Cell 18:399–402

    CAS  PubMed  Google Scholar 

  • Gossett LA, Kelvin DJ, Sternberg EA, Olson EN (1989) A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes. Mol Cell Biol 9:5022–5033

    CAS  PubMed  Google Scholar 

  • Gottlieb PD, Pierce SA, Sims RJ, Yamagishi H, Weihe EK, Harriss JV, Maika SD, Kuziel WA, King HL, Olson EN et al (2002) Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis. Nat Genet 31:25–32

    CAS  PubMed  Google Scholar 

  • Harvey RP (1996) NK-2 homeobox genes and heart development. Dev Biol 178:203–216

    CAS  PubMed  Google Scholar 

  • He A, Kong SW, Ma Q, Pu WT (2011) Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart. Proc Natl Acad Sci USA 108:5632–5637

    CAS  PubMed  Google Scholar 

  • Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, Komuro I (2001) Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Nat Genet 28:276–280

    CAS  PubMed  Google Scholar 

  • Ho L, Crabtree GR (2010) Chromatin remodelling during development. Nature 463:474–484

    CAS  PubMed  Google Scholar 

  • Hong S, Cho YW, Yu LR, Yu H, Veenstra TD, Ge K (2007) Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc Natl Acad Sci USA 104:18439–18444

    CAS  PubMed  Google Scholar 

  • Inagawa M, Nakajima K, Makino T, Ogawa S, Kojima M, Ito S, Ikenishi A, Hayashi T, Schwartz RJ, Nakamura K et al (2013) Histone H3 lysine 9 methyltransferases, G9a and GLP are essential for cardiac morphogenesis. Mech Dev 130:519–531

    CAS  PubMed  Google Scholar 

  • Jiang Y, Drysdale TA, Evans T (1999) A role for GATA-4/5/6 in the regulation of Nkx2.5 expression with implications for patterning of the precardiac field. Dev Biol 216:57–71

    CAS  PubMed  Google Scholar 

  • Kirk EP, Sunde M, Costa MW, Rankin SA, Wolstein O, Castro ML, Butler TL, Hyun C, Guo G, Otway R et al (2007) Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy. Am J Hum Genet 81:280–291

    CAS  PubMed  Google Scholar 

  • Kitajima S, Takagi A, Inoue T, Saga Y (2000) MesP1 and MesP2 are essential for the development of cardiac mesoderm. Development 127:3215–3226

    CAS  PubMed  Google Scholar 

  • Klaus A, Saga Y, Taketo MM, Tzahor E, Birchmeier W (2007) Distinct roles of Wnt/beta-catenin and Bmp signaling during early cardiogenesis. Proc Natl Acad Sci USA 104:18531–18536

    CAS  PubMed  Google Scholar 

  • Klose RJ, Zhang Y (2007) Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol 8:307–318

    CAS  PubMed  Google Scholar 

  • Kohli RM, Zhang Y (2013) TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502:472–479

    CAS  PubMed  Google Scholar 

  • Komuro I, Izumo S (1993) Csx: a murine homeobox-containing gene specifically expressed in the developing heart. Proc Natl Acad Sci USA 90:8145–8149

    CAS  PubMed  Google Scholar 

  • Kuo CT, Morrisey EE, Anandappa R, Sigrist K, Lu MM, Parmacek MS, Soudais C, Leiden JM (1997) GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev 11:1048–1060

    CAS  PubMed  Google Scholar 

  • Kwon C, Arnold J, Hsiao EC, Taketo MM, Conklin BR, Srivastava D (2007) Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors. Proc Natl Acad Sci USA 104:10894–10899

    CAS  PubMed  Google Scholar 

  • Kwon C, Qian L, Cheng P, Nigam V, Arnold J, Srivastava D (2009) A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate. Nat Cell Biol 11:951–957

    CAS  PubMed  Google Scholar 

  • Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E et al (2007) A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449:689–694

    CAS  PubMed  Google Scholar 

  • Lee S, Lee JW, Lee SK (2012) UTX, a histone H3-lysine 27 demethylase, acts as a critical switch to activate the cardiac developmental program. Dev Cell 22:25–37

    CAS  PubMed  Google Scholar 

  • Lepore JJ, Mericko PA, Cheng L, Lu MM, Morrisey EE, Parmacek MS (2006) GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis. J Clin Invest 116:929–939

    CAS  PubMed  Google Scholar 

  • Li E, Bestor TH, Jaenisch R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915–926

    CAS  PubMed  Google Scholar 

  • Lien CL, Wu C, Mercer B, Webb R, Richardson JA, Olson EN (1999) Control of early cardiac-specific transcription of Nkx2-5 by a GATA-dependent enhancer. Development 126:75–84

    CAS  PubMed  Google Scholar 

  • Lin Q, Schwarz J, Bucana C, Olson EN (1997) Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C. Science 276:1404–1407

    CAS  PubMed  Google Scholar 

  • Lin Q, Lu J, Yanagisawa H, Webb R, Lyons GE, Richardson JA, Olson EN (1998) Requirement of the MADS-box transcription factor MEF2C for vascular development. Development 125:4565–4574

    CAS  PubMed  Google Scholar 

  • Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP (1993) Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development 119:969

    CAS  PubMed  Google Scholar 

  • Lickert H, Takeuchi JK, Von Both I, Walls JR, McAuliffe F, Adamson SL, Henkelman RM, Wrana JL, Rossant J, Bruneau BG (2004) Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432:107–112

    CAS  PubMed  Google Scholar 

  • Lubitz S, Glaser S, Schaft J, Stewart AF, Anastassiadis K (2007) Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase Mll2. Mol Biol Cell 18:2356–2366

    CAS  PubMed  Google Scholar 

  • Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389(6648):251–260

    CAS  PubMed  Google Scholar 

  • Lyons I, Parsons LM, Hartley L, Li R, Andrews JE, Robb L, Harvey RP (1995) Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev 9:1654–1666

    CAS  PubMed  Google Scholar 

  • Mao Z, Bonni A, Xia F, Nadal-Vicens M, Greenberg ME (1999) Neuronal activity-dependent cell survival mediated by transcription factor MEF2. Science 286:785–790

    CAS  PubMed  Google Scholar 

  • Martin C, Zhang Y (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6:838–849

    CAS  PubMed  Google Scholar 

  • Massari ME, Murre C (2000) Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 20:429–440

    CAS  PubMed  Google Scholar 

  • McFadden DG, Charite J, Richardson JA, Srivastava D, Firulli AB, Olson EN (2000) A GATA-dependent right ventricular enhancer controls dHAND transcription in the developing heart. Development 127:5331–5341

    CAS  PubMed  Google Scholar 

  • McKinsey TA (2012) Therapeutic potential for HDAC inhibitors in the heart. Annu Rev Pharmacol Toxicol 52:303–319

    CAS  PubMed  Google Scholar 

  • Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S et al (2001) TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104:619–629

    CAS  PubMed  Google Scholar 

  • Miller SA, Mohn SE, Weinmann AS (2010) Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression. Mol Cell 40:594–605

    CAS  PubMed  Google Scholar 

  • Mohan RA, van Engelen K, Stefanovic S, Barnett P, Ilgun A, Baars MJ, Bouma BJ, Mulder BJ, Christoffels VM, Postma AV (2014) A mutation in the Kozak sequence of GATA4 hampers translation in a family with atrial septal defects. Am J Med Genet A 164A:2732–2738

    PubMed  Google Scholar 

  • Molkentin JD, Lin Q, Duncan SA, Olson EN (1997) Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev 11:1061–1072

    CAS  PubMed  Google Scholar 

  • Molkentin JD (2000) The zinc finger-containing transcription factors GATA-4, -5, and -6. Ubiquitously expressed regulators of tissue-specific gene expression. J Biol Chem 275:38949–38952

    CAS  PubMed  Google Scholar 

  • Mommersteeg MT, Dominguez JN, Wiese C, Norden J, de Gier-de Vries C, Burch JB, Kispert A, Brown NA, Moorman AF, Christoffels VM (2010) The sinus venosus progenitors separate and diversify from the first and second heart fields early in development. Cardiovasc Res 87:92–101

    CAS  PubMed  Google Scholar 

  • Mori AD, Bruneau BG (2004) TBX5 mutations and congenital heart disease: Holt-Oram syndrome revealed. Curr Opin Cardiol 19:211–215

    PubMed  Google Scholar 

  • Morrisey EE, Tang Z, Sigrist K, Lu MM, Jiang F, Ip HS, Parmacek MS (1998) GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo. Genes Dev 12:3579–3590

    CAS  PubMed  Google Scholar 

  • Naito AT, Shiojima I, Akazawa H, Hidaka K, Morisaki T, Kikuchi A, Komuro I (2006) Developmental stage-specific biphasic roles of Wnt/beta-catenin signaling in cardiomyogenesis and hematopoiesis. Proc Natl Acad Sci USA 103:19812–19817

    CAS  PubMed  Google Scholar 

  • Naya FJ, Black BL, Wu H, Bassel-Duby R, Richardson JA, Hill JA, Olson EN (2002) Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat Med 8:1303–1309

    CAS  PubMed  Google Scholar 

  • Nemer G, Nemer M (2001) Regulation of heart development and function through combinatorial interactions of transcription factors. Ann Med 33:604–610

    CAS  PubMed  Google Scholar 

  • Nemer G, Nemer M (2003) Transcriptional activation of BMP-4 and regulation of mammalian organogenesis by GATA-4 and -6. Dev Biol 254:131–148

    CAS  PubMed  Google Scholar 

  • Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC et al (2010) Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 42:790–793

    CAS  PubMed  Google Scholar 

  • Ohtani K, Zhao C, Dobreva G, Manavski Y, Kluge B, Braun T, Rieger MA, Zeiher AM, Dimmeler S (2013) Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem cells. Circ Res 113:856–862

    CAS  PubMed  Google Scholar 

  • Oka T, Maillet M, Watt AJ, Schwartz RJ, Aronow BJ, Duncan SA, Molkentin JD (2006) Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ Res 98:837–845

    CAS  PubMed  Google Scholar 

  • Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257

    CAS  PubMed  Google Scholar 

  • Olson EN (2006) Gene regulatory networks in the evolution and development of the heart. Science 313:1922–1927

    CAS  PubMed  Google Scholar 

  • Orkin SH, Shivdasani RA, Fujiwara Y, McDevitt MA (1998) Transcription factor GATA-1 in megakaryocyte development. Stem Cells 16(Suppl 2):79–83

    PubMed  Google Scholar 

  • Paige SL, Thomas S, Stoick-Cooper CL, Wang H, Maves L, Sandstrom R, Pabon L, Reinecke H, Pratt G, Keller G et al (2012) A temporal chromatin signature in human embryonic stem cells identifies regulators of cardiac development. Cell 151:221–232

    CAS  PubMed  Google Scholar 

  • Pan G, Tian S, Nie J, Yang C, Ruotti V, Wei H, Jonsdottir GA, Stewart R, Thomson JA (2007) Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell 1:299–312

    CAS  PubMed  Google Scholar 

  • Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, Evans SM, Clark B, Feramisco JR, Giles W et al (2004) Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 117:373–386

    CAS  PubMed  Google Scholar 

  • Phan D, Rasmussen TL, Nakagawa O, McAnally J, Gottlieb PD, Tucker PW, Richardson JA, Bassel-Duby R, Olson EN (2005) BOP, a regulator of right ventricular heart development, is a direct transcriptional target of MEF2C in the developing heart. Development 132:2669–2678

    CAS  PubMed  Google Scholar 

  • Pikkarainen S, Tokola H, Kerkela R, Ruskoaho H (2004) GATA transcription factors in the developing and adult heart. Cardiovasc Res 63:196–207

    CAS  PubMed  Google Scholar 

  • Postma AV, van de Meerakker JB, Mathijssen IB, Barnett P, Christoffels VM, Ilgun A, Lam J, Wilde AA, Lekanne Deprez RH, Moorman AF (2008) A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ Res 102:1433–1442

    CAS  PubMed  Google Scholar 

  • Prall OW, Menon MK, Solloway MJ, Watanabe Y, Zaffran S, Bajolle F, Biben C, McBride JJ, Robertson BR, Chaulet H et al (2007) An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell 128:947–959

    CAS  PubMed  Google Scholar 

  • Pu WT, Ishiwata T, Juraszek AL, Ma Q, Izumo S (2004) GATA4 is a dosage-sensitive regulator of cardiac morphogenesis. Dev Biol 275:235–244

    CAS  PubMed  Google Scholar 

  • Reamon-Buettner SM, Borlak J (2004) TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed hearts. Hum Mutat 24:104

    PubMed  Google Scholar 

  • Reecy JM, Li X, Yamada M, DeMayo FJ, Newman CS, Harvey RP, Schwartz RJ (1999) Identification of upstream regulatory regions in the heart-expressed homeobox gene Nkx2-5. Development 126:839–849

    CAS  PubMed  Google Scholar 

  • Reiter JF, Alexander J, Rodaway A, Yelon D, Patient R, Holder N, Stainier DY (1999) Gata5 is required for the development of the heart and endoderm in zebrafish. Genes Dev 13:2983–2995

    CAS  PubMed  Google Scholar 

  • Reyes JC, Barra J, Muchardt C, Camus A, Babinet C, Yaniv M (1998) Altered control of cellular proliferation in the absence of mammalian brahma (SNF2alpha). EMBO J 17:6979–6991

    CAS  PubMed  Google Scholar 

  • Saga Y, Miyagawa-Tomita S, Takagi A, Kitajima S, Miyazaki J, Inoue T (1999) MesP1 is expressed in the heart precursor cells and required for the formation of a single heart tube. Development 126:3437–3447

    CAS  PubMed  Google Scholar 

  • Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, Seidman JG (1998) Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 281:108–111

    CAS  PubMed  Google Scholar 

  • Shen T, Aneas I, Sakabe N, Dirschinger RJ, Wang G, Smemo S, Westlund JM, Cheng H, Dalton N, Gu Y et al (2011) Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function. J Clin Invest 121:4640–4654

    CAS  PubMed  Google Scholar 

  • Shpargel KB, Starmer J, Yee D, Pohlers M, Magnuson T (2014) KDM6 demethylase independent loss of histone H3 lysine 27 trimethylation during early embryonic development. PLoS Genet 10, e1004507

    PubMed  Google Scholar 

  • Simon JA, Kingston RE (2013) Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol Cell 49:808–824

    CAS  PubMed  Google Scholar 

  • Singh MK, Christoffels VM, Dias JM, Trowe MO, Petry M, Schuster-Gossler K, Burger A, Ericson J, Kispert A (2005) Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2. Development 132:2697–2707

    CAS  PubMed  Google Scholar 

  • Soufi A, Donahue G, Zaret KS (2012) Facilitators and impediments of the pluripotency reprogramming factors’ initial engagement with the genome. Cell 151:994–1004

    CAS  PubMed  Google Scholar 

  • Sridharan R, Gonzales-Cope M, Chronis C, Bonora G, McKee R, Huang C, Patel S, Lopez D, Mishra N, Pellegrini M et al (2013) Proteomic and genomic approaches reveal critical functions of H3K9 methylation and heterochromatin protein-1Îł in reprogramming to pluripotency. Nat Cell Biol 15:872–882

    CAS  PubMed  Google Scholar 

  • Srivastava D, Cserjesi P, Olson EN (1995) A subclass of bHLH proteins required for cardiac morphogenesis. Science 270:1995–1999

    CAS  PubMed  Google Scholar 

  • Srivastava D, Thomas T, Lin Q, Kirby ML, Brown D, Olson EN (1997) Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet 16:154–160

    CAS  PubMed  Google Scholar 

  • Srivastava D (2006) Making or breaking the heart: from lineage determination to morphogenesis. Cell 126:1037–1048

    CAS  PubMed  Google Scholar 

  • Stallmeyer B, Fenge H, Nowak-Gottl U, Schulze-Bahr E (2010) Mutational spectrum in the cardiac transcription factor gene NKX2.5 (CSX) associated with congenital heart disease. Clin Genet 78:533–540

    CAS  PubMed  Google Scholar 

  • Stanley EG, Biben C, Elefanty A, Barnett L, Koentgen F, Robb L, Harvey RP (2002) Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3′UTR-ires-Cre allele of the homeobox gene Nkx2-5. Int J Dev Biol 46:431–439

    CAS  PubMed  Google Scholar 

  • Stennard FA, Costa MW, Elliott DA, Rankin S, Haast SJ, Lai D, McDonald LP, Niederreither K, Dolle P, Bruneau BG et al (2003) Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Dev Biol 262:206–224

    CAS  PubMed  Google Scholar 

  • Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H et al (2002) G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev 16:1779–1791

    CAS  PubMed  Google Scholar 

  • Tachibana M, Ueda J, Fukuda M, Takeda N, Ohta T, Iwanari H, Sakihama T, Kodama T, Hamakubo T, Shinkai Y (2005) Histone methyltransferases G9a and GLP form heteromeric complexes and are both crucial for methylation of euchromatin at H3-K9. Genes Dev 19:815–826

    CAS  PubMed  Google Scholar 

  • Takeuchi JK, Lou X, Alexander JM, Sugizaki H, Delgado-OlguĂ­n P, Holloway AK, Mori AD, Wylie JN, Munson C, Zhu Y et al (2011) Chromatin remodelling complex dosage modulates transcription factor function in heart development. Nat Commun 2:187

    PubMed  Google Scholar 

  • Tam PP, Parameswaran M, Kinder SJ, Weinberger RP (1997) The allocation of epiblast cells to the embryonic heart and other mesodermal lineages: the role of ingression and tissue movement during gastrulation. Development 124:1631–1642

    CAS  PubMed  Google Scholar 

  • Tan X, Rotllant J, Li H, De Deyne P, Du SJ (2006) SmyD1, a histone methyltransferase, is required for myofibril organization and muscle contraction in zebrafish embryos. Proc Natl Acad Sci USA 103:2713–2718

    CAS  PubMed  Google Scholar 

  • von Both I, Silvestri C, Erdemir T, Lickert H, Walls JR, Henkelman RM, Rossant J, Harvey RP, Attisano L, Wrana JL (2004) Foxh1 is essential for development of the anterior heart field. Dev Cell 7:331–345

    Google Scholar 

  • Wamstad JA, Alexander JM, Truty RM, Shrikumar A, Li F, Eilertson KE, Ding H, Wylie JN, Pico AR, Capra JA et al (2012) Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage. Cell 151:206–220

    CAS  PubMed  Google Scholar 

  • Wang C, Lee JE, Cho YW, Xiao Y, Jin Q, Liu C, Ge K (2012) UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity. Proc Natl Acad Sci USA 109:15324–15329

    CAS  PubMed  Google Scholar 

  • Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M et al (2006) Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125:467–481

    CAS  PubMed  Google Scholar 

  • Wissmann M, Yin N, MĂĽller JM, Greschik H, Fodor BD, Jenuwein T, Vogler C, Schneider R, GĂĽnther T, Buettner R et al (2007) Cooperative demethylation by JMJD2C and LSD1 promotes androgen receptor-dependent gene expression. Nat Cell Biol 9:347–353

    CAS  PubMed  Google Scholar 

  • Xiang R, Fan LL, Huang H, Cao BB, Li XP, Peng DQ, Xia K (2013) A novel mutation of GATA4 (K319E) is responsible for familial atrial septal defect and pulmonary valve stenosis. Gene 534:320–323

    Google Scholar 

  • Xin M, Davis CA, Molkentin JD, Lien CL, Duncan SA, Richardson JA, Olson EN (2006) A threshold of GATA4 and GATA6 expression is required for cardiovascular development. Proc Natl Acad Sci USA 103:11189–11194

    CAS  PubMed  Google Scholar 

  • Xu H, Morishima M, Wylie JN, Schwartz RJ, Bruneau BG, Lindsay EA, Baldini A (2004) Tbx1 has a dual role in the morphogenesis of the cardiac outflow tract. Development 131:3217–3227

    CAS  PubMed  Google Scholar 

  • Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, Minoshima S, Ichida F, Joo K, Kimura M, Imamura S et al (2003) Role of TBX1 in human del22q11.2 syndrome. Lancet 362:1366–1373

    CAS  PubMed  Google Scholar 

  • Yamada M, Revelli JP, Eichele G, Barron M, Schwartz RJ (2000) Expression of chick Tbx-2, Tbx-3, and Tbx-5 genes during early heart development: evidence for BMP2 induction of Tbx2. Dev Biol 228:95–105

    CAS  PubMed  Google Scholar 

  • Yamagishi H, Olson EN, Srivastava D (2000) The basic helix-loop-helix transcription factor, dHAND, is required for vascular development. J Clin Invest 105:261–270

    CAS  PubMed  Google Scholar 

  • Yamane K, Tateishi K, Klose RJ, Fang J, Fabrizio LA, Erdjument-Bromage H, Taylor-Papadimitriou J, Tempst P, Zhang Y (2007) PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Mol Cell 25:801–812

    CAS  PubMed  Google Scholar 

  • Zeisberg EM, Ma Q, Juraszek AL, Moses K, Schwartz RJ, Izumo S, Pu WT (2005) Morphogenesis of the right ventricle requires myocardial expression of Gata4. J Clin Invest 115:1522–1531

    CAS  PubMed  Google Scholar 

  • Zhao R, Watt AJ, Li J, Luebke-Wheeler J, Morrisey EE, Duncan SA (2005) GATA6 is essential for embryonic development of the liver but dispensable for early heart formation. Mol Cell Biol 25:2622–2631

    CAS  PubMed  Google Scholar 

  • Zhao R, Watt AJ, Battle MA, Li J, Bondow BJ, Duncan SA (2008) Loss of both GATA4 and GATA6 blocks cardiac myocyte differentiation and results in acardia in mice. Dev Biol 317:614–619

    CAS  PubMed  Google Scholar 

  • Zhao XD, Han X, Chew JL, Liu J, Chiu KP, Choo A, Orlov YL, Sung WK, Shahab A, Kuznetsov VA et al (2007) Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell 1:286–298

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Andrew Riching for critical reading. X.M. was supported by NIH (R01HL132211). K.S was supported by NIH (R01HL133230), American Heart Association (13SDG17400031), and Boettcher Foundation.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH, 45229, USA

    Mei Xin

  2. Division of Cardiology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA

    Kunhua Song

  3. Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado School of Medicine, Aurora, CO, 80045, USA

    Kunhua Song

Authors
  1. Mei Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kunhua Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mei Xin or Kunhua Song .

Editor information

Editors and Affiliations

  1. Department of Molecular, Cardiology and Epigenetics, University of Heidelberg, Heidelberg, Germany

    Johannes Backs

  2. Department of Medicine, Division of Cardiology, University of Colorado Denver, Aurora, CO, USA

    Timothy A. McKinsey

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Xin, M., Song, K. (2016). Epigenetic Regulations in Cardiac Development. In: Backs, J., McKinsey, T.A. (eds) Epigenetics in Cardiac Disease. Cardiac and Vascular Biology, vol 1. Springer, Cham. https://doi.org/10.1007/978-3-319-41457-7_3

Download citation

Publish with us

Policies and ethics

Search

Navigation