Skip to main content
SpringerLink
Log in

Epigenetic regulation of retinal development and disease

  • Published:
Journal of Ocular Biology, Diseases, and Informatics

Abstract

Epigenetic regulation, including DNA methylation, histone modifications, and chromosomal organization, is emerging as a new layer of transcriptional regulation in retinal development and maintenance. Guided by intrinsic transcription factors and extrinsic signaling molecules, epigenetic regulation can activate and/or repress the expression of specific sets of genes, therefore playing an important role in retinal cell fate specification and terminal differentiation during development as well as maintaining cell function and survival in adults. Here, we review the major findings that have linked these mechanisms to the development and maintenance of retinal structure and function, with a focus on ganglion cells and photoreceptors. The mechanisms of epigenetic regulation are highly complex and vary among different cell types. Understanding the basic principles of these mechanisms and their regulatory pathways may provide new insight into the pathogenesis of retinal diseases associated with transcription dysregulation, and new therapeutic strategies for treatment.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

HKM:

Histone lysine methylation

HKMTase:

Histone methyltransferase

HKDMase:

Histone lysine demethylase

DNMTase:

DNA methyltransferase

HAT (KAT):

Histone lysine acetyltransferase

HDAC:

Histone deacetylase

CT:

Chromatin territory

TxF:

Transcription factory

References

  1. Humphries MM, et al. Retinopathy induced in mice by targeted disruption of the rhodopsin gene [see comments]. Nat Genet. 1997;15:216–9.

    Article  PubMed  CAS  Google Scholar 

  2. Olsson JE, et al. Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa. Neuron. 1992;9:815–30.

    Article  PubMed  CAS  Google Scholar 

  3. Guo Y, et al. Early gene expression changes in the retinal ganglion cell layer of a rat glaucoma model. Investig Ophthalmol Vis Sci. 2011;52:1460–73.

    Article  CAS  Google Scholar 

  4. Wang DY, et al. Global gene expression changes in rat retinal ganglion cells in experimental glaucoma. Investig Ophthalmol Vis Sci. 2010;51:4084–95.

    Article  Google Scholar 

  5. Panagis L, et al. Gene expression changes in areas of focal loss of retinal ganglion cells in the retina of DBA/2J mice. Investig Ophthalmol Vis Sci. 2010;51:2024–34.

    Article  Google Scholar 

  6. Hennig AK, Peng GH, Chen S. Regulation of photoreceptor gene expression by Crx-associated transcription factor network. Brain Res. 2008;1192:114–33.

    Article  PubMed  CAS  Google Scholar 

  7. Swaroop A, Kim D, Forrest D. Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nat Rev Neurosci. 2010;11:563–76.

    Article  PubMed  CAS  Google Scholar 

  8. Ohsawa R, Kageyama R. Regulation of retinal cell fate specification by multiple transcription factors. Brain research. 2008;1192:90–8.

    Article  PubMed  CAS  Google Scholar 

  9. Zhou VW, Goren A, Bernstein BE. Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet. 2011;12:7–18.

    Article  PubMed  CAS  Google Scholar 

  10. Walton EL, Francastel C, & Velasco G (2011) Maintenance of DNA methylation: Dnmt3b joins the dance. Epigenetics 6.

  11. Peng GH, Chen S. Active opsin loci adopt intrachromosomal loops that depend on the photoreceptor transcription factor network. Proc Natl Acad Sci U S A. 2011;108:17821–6.

    Article  PubMed  CAS  Google Scholar 

  12. Wang Y, et al. A locus control region adjacent to the human red and green visual pigment genes. Neuron. 1992;9:429–40.

    Article  PubMed  CAS  Google Scholar 

  13. Wang Y, et al. Mutually exclusive expression of human red and green visual pigment-reporter transgenes occurs at high frequency in murine cone photoreceptors. Proc Natl Acad Sci U S A. 1999;96:5251–6.

    Article  PubMed  CAS  Google Scholar 

  14. Chakalova L, et al. Developmental regulation of the beta-globin gene locus. Prog Mol Subcell Biol. 2005;38:183–206.

    Article  PubMed  CAS  Google Scholar 

  15. Huang J, et al. Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1. J Virol. 2006;80:5740–6.

    Article  PubMed  CAS  Google Scholar 

  16. Rao RC, et al. Dynamic patterns of histone lysine methylation in the developing retina. Invest Ophthalmol Vis Sci. 2010;51:6784–92.

    Article  PubMed  Google Scholar 

  17. Shi Y, et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004;119:941–53.

    Article  PubMed  CAS  Google Scholar 

  18. Skowronska-Krawczyk D, Ballivet M, Dynlacht BD, Matter JM. Highly specific interactions between bHLH transcription factors and chromatin during retina development. Development. 2004;131:4447–54.

    Article  PubMed  CAS  Google Scholar 

  19. Tachibana M, et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 2002;16:1779–91.

    Article  PubMed  CAS  Google Scholar 

  20. Cherrier T, et al. p21(WAF1) gene promoter is epigenetically silenced by CTIP2 and SUV39H1. Oncogene. 2009;28:3380–9.

    Article  PubMed  CAS  Google Scholar 

  21. Eom GH, et al. Histone methyltransferase PRDM8 regulates mouse testis steroidogenesis. Biochem Biophys Res Commun. 2009;388:131–6.

    Article  PubMed  CAS  Google Scholar 

  22. Komai T, Iwanari H, Mochizuki Y, Hamakubo T, Shinkai Y. Expression of the mouse PR domain protein Prdm8 in the developing central nervous system. Gene Expr Patterns. 2009;9:503–14.

    Article  PubMed  CAS  Google Scholar 

  23. Kubicek S, et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell. 2007;25:473–81.

    Article  PubMed  CAS  Google Scholar 

  24. Greiner D, Bonaldi T, Eskeland R, Roemer E, Imhof A. Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9. Nat Chem Biol. 2005;1:143–5.

    Article  PubMed  CAS  Google Scholar 

  25. Toth Z, et al. Epigenetic analysis of KSHV latent and lytic genomes. PLoS pathogens. 2010;6:e1001013.

    Article  PubMed  CAS  Google Scholar 

  26. Tan J, et al. Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene repression selectively induces apoptosis in cancer cells. Genes Dev. 2007;21:1050–63.

    Article  PubMed  CAS  Google Scholar 

  27. Schermelleh L, et al. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res. 2007;35:4301–12.

    Article  PubMed  CAS  Google Scholar 

  28. Nasonkin IO, et al. Distinct nuclear localization patterns of DNA methyltransferases in developing and mature mammalian retina. J Comp Neurol. 2011;519:1914–30.

    Article  PubMed  CAS  Google Scholar 

  29. Nasonkin IO, et al. (2010) Role of Epigenetics (DNA Methylation) in RPE and Photoreceptor Development. in Invest Ophthalmol Vis Sci (Annual Meeting Abstracts), pp E-Abstract 4304.

  30. Patel K, et al. (2011) The role of Dnmt1 in retinal differentiation. in Invest Ophthalmol Vis Sci (Annual Meeting Abstracts), pp E-Abstract 5982-A5131.

  31. Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999;99:247–57.

    Article  PubMed  CAS  Google Scholar 

  32. Bedford DC, Kasper LH, Fukuyama T, Brindle PK. Target gene context influences the transcriptional requirement for the KAT3 family of CBP and p300 histone acetyltransferases. Epigenetics. 2010;5:9–15.

    Article  PubMed  CAS  Google Scholar 

  33. Das C, Lucia MS, Hansen KC, Tyler JK. CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature. 2009;459:113–7.

    Article  PubMed  CAS  Google Scholar 

  34. McManus KJ, Hendzel MJ. Quantitative analysis of CBP- and P300-induced histone acetylations in vivo using native chromatin. Mol Cell Biol. 2003;23:7611–27.

    Article  PubMed  CAS  Google Scholar 

  35. Jin Q, et al. Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J. 2011;30:249–62.

    Article  PubMed  CAS  Google Scholar 

  36. Gaub P, et al. The histone acetyltransferase p300 promotes intrinsic axonal regeneration. Brain. 2011;134:2134–48.

    Article  PubMed  Google Scholar 

  37. Li X, Kazgan N. Mammalian sirtuins and energy metabolism. Int J Biol Sci. 2011;7:575–87.

    Article  PubMed  CAS  Google Scholar 

  38. Verdin E, Dequiedt F, Kasler HG. Class II histone deacetylases: versatile regulators. Trends Genet. 2003;19:286–93.

    Article  PubMed  CAS  Google Scholar 

  39. Geranton SM (2011) Targeting epigenetic mechanisms for pain relief. Curr Opin Pharmacol.

  40. Pelzel HR, Schlamp CL, Nickells RW. Histone H4 deacetylation plays a critical role in early gene silencing during neuronal apoptosis. BMC Neurosci. 2010;11:62.

    Article  PubMed  CAS  Google Scholar 

  41. Chen B, Cepko CL. Requirement of histone deacetylase activity for the expression of critical photoreceptor genes. BMC Dev Biol. 2007;7:78.

    Article  PubMed  CAS  Google Scholar 

  42. Jensen DE, et al. BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene. 1998;16:1097–112.

    Article  PubMed  CAS  Google Scholar 

  43. Scheuermann JC, et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature. 2010;465:243–7.

    Article  PubMed  CAS  Google Scholar 

  44. Harbour JW, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330:1410–3.

    Article  PubMed  CAS  Google Scholar 

  45. Goldstein AM. Germline BAP1 mutations and tumor susceptibility. Nat Genet. 2011;43:925–6.

    Article  PubMed  CAS  Google Scholar 

  46. Lang G, et al. The tightly controlled deubiquitination activity of the human SAGA complex differentially modifies distinct gene regulatory elements. Mol Cell Biol. 2011;31:3734–44.

    Article  PubMed  CAS  Google Scholar 

  47. Henikoff S, Shilatifard A. Histone modification: cause or cog? Trends Genet. 2011;27:389–96.

    Article  PubMed  CAS  Google Scholar 

  48. Guillemette B, et al. Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning. PLoS biology. 2005;3:e384.

    Article  PubMed  CAS  Google Scholar 

  49. Segal E, et al. A genomic code for nucleosome positioning. Nature. 2006;442:772–8.

    Article  PubMed  CAS  Google Scholar 

  50. Cremer T, Cremer M. Chromosome territories. Cold Spring Harbor perspect in biol. 2010;2:a003889.

    Article  CAS  Google Scholar 

  51. Hakim O, Sung MH, Hager GL. 3D shortcuts to gene regulation. Curr Opin Cell Biol. 2010;22:305–13.

    Article  PubMed  CAS  Google Scholar 

  52. Rapicavoli NA, Poth EM, Zhu H, Blackshaw S. The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity. Neural development. 2011;6:32.

    Article  PubMed  CAS  Google Scholar 

  53. Rapicavoli NA, Poth EM, Blackshaw S. The long noncoding RNA RNCR2 directs mouse retinal cell specification. BMC Dev Biol. 2010;10:49.

    Article  PubMed  CAS  Google Scholar 

  54. Gupta RA, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.

    Article  PubMed  CAS  Google Scholar 

  55. Hung T, Chang HY. Long noncoding RNA in genome regulation: prospects and mechanisms. RNA Biol. 2010;7:582–5.

    Article  PubMed  CAS  Google Scholar 

  56. Rapicavoli NA, Blackshaw S. New meaning in the message: noncoding RNAs and their role in retinal development. Dev Dyn. 2009;238:2103–14.

    Article  PubMed  CAS  Google Scholar 

  57. Orom UA, Shiekhattar R. Noncoding RNAs and enhancers: complications of a long-distance relationship. Trends Genet. 2011;27:433–9.

    Article  PubMed  CAS  Google Scholar 

  58. Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322:750–6.

    Article  PubMed  CAS  Google Scholar 

  59. Lan F, et al. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007;449:689–94.

    Article  PubMed  CAS  Google Scholar 

  60. Mikkelsen TS, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007;448:553–60.

    Article  PubMed  CAS  Google Scholar 

  61. Chen DF, Schneider GE, Martinou JC, Tonegawa S. Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature. 1997;385:434–9.

    Article  PubMed  CAS  Google Scholar 

  62. Brown NL, Patel S, Brzezinski J, Glaser T. Math5 is required for retinal ganglion cell and optic nerve formation. Development. 2001;128:2497–508.

    PubMed  CAS  Google Scholar 

  63. Matter-Sadzinski L, Matter JM, Ong MT, Hernandez J, Ballivet M. Specification of neurotransmitter receptor identity in developing retina: the chick ATH5 promoter integrates the positive and negative effects of several bHLH proteins. Development. 2001;128:217–31.

    PubMed  CAS  Google Scholar 

  64. Solovei I, et al. Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell. 2009;137:356–68.

    Article  PubMed  CAS  Google Scholar 

  65. Sher F, et al. Differentiation of neural stem cells into oligodendrocytes: involvement of the polycomb group protein Ezh2. Stem Cells. 2008;26:2875–83.

    Article  PubMed  CAS  Google Scholar 

  66. Hirabayashi Y, et al. Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. Neuron. 2009;63:600–13.

    Article  PubMed  CAS  Google Scholar 

  67. Maze I, et al. Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science. 2010;327:213–6.

    Article  PubMed  CAS  Google Scholar 

  68. Ding N, et al. MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression. J Biol Chem. 2009;284:2648–56.

    Article  PubMed  CAS  Google Scholar 

  69. Huang S, Shao G, Liu L. The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. J Biol Chem. 1998;273:15933–9.

    Article  PubMed  CAS  Google Scholar 

  70. Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986;321:209–13.

    Article  PubMed  CAS  Google Scholar 

  71. Meissner A, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008;454:766–70.

    PubMed  CAS  Google Scholar 

  72. Laurent L, et al. Dynamic changes in the human methylome during differentiation. Genome Res. 2010;20:320–31.

    Article  PubMed  CAS  Google Scholar 

  73. Denis H, Ndlovu MN, Fuks F. Regulation of mammalian DNA methyltransferases: a route to new mechanisms. EMBO Rep. 2011;12:647–56.

    Article  PubMed  CAS  Google Scholar 

  74. Nguyen CT, et al. Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2'-deoxycytidine. Cancer Res. 2002;62:6456–61.

    PubMed  CAS  Google Scholar 

  75. Xin Z, et al. Role of histone methyltransferase G9a in CpG methylation of the Prader–Willi syndrome imprinting center. J Biol Chem. 2003;278:14996–5000.

    Article  PubMed  CAS  Google Scholar 

  76. Lehnertz B, et al. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr Biol. 2003;13:1192–200.

    Article  PubMed  CAS  Google Scholar 

  77. Wang J, et al. The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat Genet. 2009;41:125–9.

    Article  PubMed  CAS  Google Scholar 

  78. Li J, et al. Structural basis for specific binding of human MPP8 chromodomain to histone H3 methylated at lysine 9. PLoS One. 2011;6:e25104.

    Article  PubMed  CAS  Google Scholar 

  79. Chang Y, et al. MPP8 mediates the interactions between DNA methyltransferase Dnmt3a and H3K9 methyltransferase GLP/G9a. Nat Commun. 2011;2:533.

    Article  PubMed  CAS  Google Scholar 

  80. Petkova TD, Seigel GM, Otteson DC. A role for DNA methylation in regulation of EphA5 receptor expression in the mouse retina. Vision Res. 2011;51:260–8.

    Article  PubMed  CAS  Google Scholar 

  81. Bevins N, Lemke G, Reber M. Genetic dissection of EphA receptor signaling dynamics during retinotopic mapping. J Neurosci. 2011;31:10302–10.

    Article  PubMed  CAS  Google Scholar 

  82. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997;389:349–52.

    Article  PubMed  CAS  Google Scholar 

  83. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705.

    Article  PubMed  CAS  Google Scholar 

  84. Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell. 2007;128:707–19.

    Article  PubMed  CAS  Google Scholar 

  85. Jones PL, Wolffe AP. Relationships between chromatin organization and DNA methylation in determining gene expression. Semin Cancer Biol. 1999;9:339–47.

    Article  PubMed  CAS  Google Scholar 

  86. Ebert A, Lein S, Schotta G, Reuter G. Histone modification and the control of heterochromatic gene silencing in Drosophila. Chromosome Res. 2006;14:377–92.

    Article  PubMed  CAS  Google Scholar 

  87. Cvekl A, Mitton KP. Epigenetic regulatory mechanisms in vertebrate eye development and disease. Heredity. 2010;105:135–51.

    Article  PubMed  CAS  Google Scholar 

  88. Yanagi Y, Masuhiro Y, Mori M, Yanagisawa J, Kato S. p300/CBP acts as a coactivator of the cone-rod homeobox transcription factor. Biochem Biophys Res Commun. 2000;269:410–4.

    Article  PubMed  CAS  Google Scholar 

  89. Peng GH, Chen S. Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation. Hum Mol Genet. 2007;16:3433–52.

    Article  CAS  Google Scholar 

  90. Chen S, et al. Interference of Crx-dependent transcription by ataxin-7 involves interaction between the glutamine regions and requires the ataxin-7 carboxy-terminal region for nuclear localization. Hum Mol Genet. 2004;13:53–67.

    Article  PubMed  CAS  Google Scholar 

  91. Palhan VB, et al. Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc Natl Acad Sci U S A. 2005;102:8472–7.

    Article  PubMed  CAS  Google Scholar 

  92. Helmlinger D, et al. Glutamine-expanded ataxin-7 alters TFTC/STAGA recruitment and chromatin structure leading to photoreceptor dysfunction. PLoS Biol. 2006;4:e67.

    Article  PubMed  CAS  Google Scholar 

  93. Anamika K, et al. Lessons from genome-wide studies: an integrated definition of the coactivator function of histone acetyl transferases. Epigenetics & chromatin. 2010;3:18.

    Article  CAS  Google Scholar 

  94. Nagy Z, Tora L. Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. Oncogene. 2007;26:5341–57.

    Article  PubMed  CAS  Google Scholar 

  95. Biermann J, et al. Valproic acid-mediated neuroprotection and regeneration in injured retinal ganglion cells. Invest Ophthalmol Vis Sci. 2010;51:526–34.

    Article  PubMed  Google Scholar 

  96. Zhang Z, et al. Valproate protects the retina from endoplasmic reticulum stress-induced apoptosis after ischemia-reperfusion injury. Neurosci Lett. 2011;504:88–92.

    Article  PubMed  CAS  Google Scholar 

  97. Biermann J, Boyle J, Pielen A, Lagreze WA. Histone deacetylase inhibitors sodium butyrate and valproic acid delay spontaneous cell death in purified rat retinal ganglion cells. Mol Vis. 2011;17:395–403.

    PubMed  CAS  Google Scholar 

  98. Gaub P, et al. HDAC inhibition promotes neuronal outgrowth and counteracts growth cone collapse through CBP/p300 and P/CAF-dependent p53 acetylation. Cell Death Differ. 2010;17:1392–408.

    Article  PubMed  CAS  Google Scholar 

  99. Clemson CM, et al. Therapeutic potential of valproic acid for retinitis pigmentosa. Br J Ophthalmol. 2011;95:89–93.

    Article  PubMed  CAS  Google Scholar 

  100. Bott M, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43:668–72.

    Article  PubMed  CAS  Google Scholar 

  101. Wiesner T, et al. Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet. 2011;43:1018–21.

    Article  PubMed  CAS  Google Scholar 

  102. Testa JR, et al. Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet. 2011;43:1022–5.

    Article  PubMed  CAS  Google Scholar 

  103. Abdel-Rahman MH, et al. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J of Medic Genetics. 2011;48:856–9.

    Article  CAS  Google Scholar 

  104. Wang H, et al. Role of histone H2A ubiquitination in Polycomb silencing. Nature. 2004;431:873–8.

    Article  PubMed  CAS  Google Scholar 

  105. Jordan G, Deeb SS, Bosten JM, Mollon JD. The dimensionality of color vision in carriers of anomalous trichromacy. J Vis. 2010;10:12.

    Article  PubMed  Google Scholar 

  106. Jordan G, Mollon JD. A study of women heterozygous for colour deficiencies. Vis Res. 1993;33:1495–508.

    Article  PubMed  CAS  Google Scholar 

  107. Boatright JH, Nickerson JM, Borst DE. Site-specific DNA hypomethylation permits expression of the IRBP gene. Brain research. 2000;887:211–21.

    Article  PubMed  CAS  Google Scholar 

  108. Bazhin AV, De Smet C, Golovastova MO, Schmidt J, Philippov PP. Aberrant demethylation of the recoverin gene is involved in the aberrant expression of recoverin in cancer cells. Exp Dermatol. 2010;19:1023–5.

    Article  PubMed  CAS  Google Scholar 

  109. Carroll J, et al. Deletion of the X-linked opsin gene array locus control region (LCR) results in disruption of the cone mosaic. Vision Res. 2010;50:1989–99.

    Article  PubMed  CAS  Google Scholar 

  110. Kizilyaprak C, Spehner D, Devys D, Schultz P. The linker histone H1C contributes to the SCA7 nuclear phenotype. Nucleus. 2011;2:444–54.

    Article  PubMed  Google Scholar 

  111. Peng G-H, Hennig AK, Chen Y, & Chen S (2010) Histone acetyltransferases CBP and p300 in photoreceptors: loss-of-function affects chromatin configuration and transcription of photoreceptor genes ARVO Meeting Abstract 51:1086.

  112. Hennig AK, Wang H, & Chen S (2010) Histone acetyltransferases cbp and p300 are required in rod photoreceptors to maintain retina structure and function ARVO Meeting Abstracts:1085.

  113. Wang Z, et al. Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell. 2009;138:1019–31.

    Article  PubMed  CAS  Google Scholar 

  114. Zhao Y, et al. A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Mol Cell. 2008;29:92–101.

    Article  PubMed  CAS  Google Scholar 

  115. Zhang XY, et al. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol Cell. 2008;29:102–11.

    Article  PubMed  CAS  Google Scholar 

  116. Abou-Sleymane G, et al. Polyglutamine expansion causes neurodegeneration by altering the neuronal differentiation program. Hum Mol Genet. 2006;15:691–703.

    Article  PubMed  CAS  Google Scholar 

  117. Chen YC, et al. (2011) Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Human molecular genetics.

  118. Bramall AN, Wright AF, Jacobson SG, McInnes RR. The genomic, biochemical, and cellular responses of the retina in inherited photoreceptor degenerations and prospects for the treatment of these disorders. Annu Rev Neurosci. 2010;33:441–72.

    Article  PubMed  CAS  Google Scholar 

  119. Sancho-Pelluz J, et al. Excessive HDAC activation is critical for neurodegeneration in the rd1 mouse. Cell death & disease. 2010;1:e24.

    Article  CAS  Google Scholar 

  120. Chen B, Cepko CL. HDAC4 regulates neuronal survival in normal and diseased retinas. Science. 2009;323:256–9.

    Article  PubMed  CAS  Google Scholar 

  121. Gasser SM, Laemmli UK. The organisation of chromatin loops: characterization of a scaffold attachment site. EMBO J. 1986;5:511–8.

    PubMed  CAS  Google Scholar 

  122. Gasser SM, Laemmli UK. Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster. Cell. 1986;46:521–30.

    Article  PubMed  CAS  Google Scholar 

  123. Paulson JR, Laemmli UK. The structure of histone-depleted metaphase chromosomes. Cell. 1977;12:817–28.

    Article  PubMed  CAS  Google Scholar 

  124. Marsden MP, Laemmli UK. Metaphase chromosome structure: evidence for a radial loop model. Cell. 1979;17:849–58.

    Article  PubMed  CAS  Google Scholar 

  125. Dekker J, Rippe K, Dekker M, Kleckner N. Capturing chromosome conformation. Science. 2002;295:1306–11.

    Article  PubMed  CAS  Google Scholar 

  126. Wurtele H, Chartrand P. Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended Chromosome Conformation Capture methodology. Chromosome Res. 2006;14:477–95.

    Article  PubMed  CAS  Google Scholar 

  127. Zhao Z, et al. Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet. 2006;38:1341–7.

    Article  PubMed  CAS  Google Scholar 

  128. Simonis M, et al. Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat Genet. 2006;38:1348–54.

    Article  PubMed  CAS  Google Scholar 

  129. Dostie J, et al. Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res. 2006;16:1299–309.

    Article  PubMed  CAS  Google Scholar 

  130. Lieberman-Aiden E, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326:289–93.

    Article  PubMed  CAS  Google Scholar 

  131. Cremer T, et al. Chromosome territoriesa functional nuclear landscape. Curr Opin Cell Biol. 2006;18:307–16.

    Article  PubMed  CAS  Google Scholar 

  132. Crutchley JL, Wang XQ, Ferraiuolo MA, Dostie J. Chromatin conformation signatures: ideal human disease biomarkers? Biomarkers in medicine. 2010;4:611–29.

    Article  PubMed  CAS  Google Scholar 

  133. Fraser J, et al. Chromatin conformation signatures of cellular differentiation. Genome Biol. 2009;10:R37.

    Article  PubMed  CAS  Google Scholar 

  134. Cremer M, et al. Multicolor 3D fluorescence in situ hybridization for imaging interphase chromosomes. Methods in molecular biol. 2008;463:205–39.

    Article  CAS  Google Scholar 

  135. Schoenfelder S, et al. Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nat Genet. 2010;42:53–61.

    Article  PubMed  CAS  Google Scholar 

  136. Zinner R, Teller K, Versteeg R, Cremer T, Cremer M. Biochemistry meets nuclear architecture: multicolor immuno-FISH for co-localization analysis of chromosome segments and differentially expressed gene loci with various histone methylations. Adv Enzym Regul. 2007;47:223–41.

    Article  CAS  Google Scholar 

  137. Boyle AP, et al. High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells. Genome Res. 2011;21:456–64.

    Article  PubMed  CAS  Google Scholar 

  138. Asp P, et al. Genome-wide remodeling of the epigenetic landscape during myogenic differentiation. Proc Natl Acad Sci U S A. 2011;108:E149–158.

    Article  PubMed  Google Scholar 

  139. Guo C, et al. Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus. Cell. 2011;147:332–43.

    Article  PubMed  CAS  Google Scholar 

  140. Akhtar A, Gasser SM. The nuclear envelope and transcriptional control. Nat Rev Genet. 2007;8:507–17.

    Article  PubMed  CAS  Google Scholar 

  141. Noordermeer D, et al. The dynamic architecture of Hox gene clusters. Science. 2011;334:222–5.

    Article  PubMed  CAS  Google Scholar 

  142. He S, et al. Chromatin organization and nuclear microenvironments in cancer cells. J Cell Biochem. 2008;104:2004–15.

    Article  PubMed  CAS  Google Scholar 

  143. Nie Z, Chen S, Kumar R, Zack DJ. RER, an evolutionarily conserved sequence upstream of the rhodopsin gene, has enhancer activity. J Biol Chem. 1996;271:2667–75.

    Article  PubMed  CAS  Google Scholar 

  144. Smallwood PM, Wang Y, Nathans J. Role of a locus control region in the mutually exclusive expression of human red and green cone pigment genes. Proc Natl Acad Sci U S A. 2002;99:1008–11.

    Article  PubMed  CAS  Google Scholar 

  145. de Melo J, Peng GH, Chen S, Blackshaw S. The Spalt family transcription factor Sall3 regulates the development of cone photoreceptors and retinal horizontal interneurons. Development. 2011;138:2325–36.

    Article  PubMed  CAS  Google Scholar 

  146. Hagege H, et al. Quantitative analysis of chromosome conformation capture assays (3C-qPCR). Nat Protoc. 2007;2:1722–33.

    Article  PubMed  CAS  Google Scholar 

  147. Kizilyaprak C, Spehner D, Devys D, Schultz P. In vivo chromatin organization of mouse rod photoreceptors correlates with histone modifications. PLoS One. 2010;5:e11039.

    Article  PubMed  CAS  Google Scholar 

  148. Gonzalo S, Blasco MA. Role of Rb family in the epigenetic definition of chromatin. Cell Cycle. 2005;4:752–5.

    Article  PubMed  CAS  Google Scholar 

  149. Eskiw CH, et al. Transcription factories and nuclear organization of the genome. Cold Spring Harbor symposia on quantitative biol. 2010;75:501–6.

    Article  CAS  Google Scholar 

  150. Eskiw C, Fraser P. Inverted rod nuclei see the light. Nature cell biol. 2009;11:680–1.

    Article  PubMed  CAS  Google Scholar 

  151. Donovan SL, Schweers B, Martins R, Johnson D, Dyer MA. Compensation by tumor suppressor genes during retinal development in mice and humans. BMC Biol. 2006;4:14.

    Article  PubMed  CAS  Google Scholar 

  152. Macaluso M, et al. Nuclear and cytoplasmic interaction of pRb2/p130 and ER-beta in MCF-7 breast cancer cells. Annals of oncol: Official J of the European Soc for Medic Oncol/ESMO 17. 2006;Suppl 7:vii27–29.

    Article  Google Scholar 

  153. Longworth MS, Dyson NJ. pRb, a local chromatin organizer with global possibilities. Chromosoma. 2010;119:1–11.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Our work presented herein was supported by grants from the National Institutes of Health (R01EY017641 to DFC, R01EY012543 to SC, R21DA024803 to DFC, P30EY02687 to WU-DOVS), Department of Veterans Affairs (1I01RX000110 to DFC), and Department of Defense (W81XWH-09-2-0091; W23RYX-9104-N603 to DFC). Additional support was provided by the American Health Foundation (to RCR), a Lew Wasserman Merit Award (to SC), and unrestricted funds from Research to Prevent Blindness (to WU-DOVS).

Author information

Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8096, St. Louis, MO, 63110, USA

    Rajesh C. Rao, Anne K. Hennig & Shiming Chen

  2. Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8096, St. Louis, MO, 63110, USA

    Shiming Chen

  3. Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

    Muhammad T. A. Malik & Dong Feng Chen

  4. VA Boston Healthcare System, 150 South Huntington Ave, Boston, MA, USA

    Dong Feng Chen

Authors
  1. Rajesh C. Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne K. Hennig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Muhammad T. A. Malik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong Feng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shiming Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shiming Chen.

Additional information

Rajesh C. Rao and Anne K. Hennig contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rao, R.C., Hennig, A.K., Malik, M.T.A. et al. Epigenetic regulation of retinal development and disease. j ocul biol dis inform 4, 121–136 (2011). https://doi.org/10.1007/s12177-012-9083-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12177-012-9083-0

Keywords

Search

Navigation