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PMID: 20671280 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Dynamic patterns of histone lysine methylation in the developing retina.

Investigative ophthalmology & visual science ·Vol. 51 ·No. 12 ·2010-12-00 ·Pages 6784-92

Rao RC, Tchedre KT, Malik MT, Coleman N, Fang Y, Marquez VE, Chen DF

Abstract

Histone lysine methylation (HKM) is an important epigenetic mechanism that establishes cell-specific gene expression and functions in development. However, epigenetic control of retinal development is poorly understood. To study the roles of HKM in retinogenesis, the authors examined the dynamic changes of three HKM modifications and of two of their regulators, the histone methyltransferases (HMTases) Ezh2 and G9a, in the mouse retina. Retinal sections and lysates from embryonic day 16 through adult were processed for immunohistochemistry and immunoblotting using antibodies against various marks and HMTases. To further analyze the biological functions of HKM, the effects of small molecule inhibitors of HMTases were examined in vitro. Methylation marks of trimethyl lysine 4 and 27 on histone H3 (H3K4me3 and H3K27me3) were detected primarily in differentiated retinal neurons in the embryonic and adult retina. In contrast, dimethyl lysine 9 on histone H3 (H3K9me2) was noted in early differentiating retinal ganglion cells but was lost after birth. The HMTases controlling H3K27me3, H3K9me2, Ezh2, and G9a were enriched in the inner embryonic retina during the period of active retinogenesis. Using the chemical inhibitors of Ezh2 and G9a, the authors reveal a role for HKM in regulating retinal neuron survival. HKM is a dynamic and spatiotemporally regulated process in the developing retina. Epigenetic regulation of gene transcription by Ezh2- and G9a-mediated HKM plays crucial roles in retinal neuron survival and may represent novel epigenetic targets to enhance viability in retinal neurodegenerative diseases such as glaucoma.

MeSH Terms
Animals Apoptosis Biomarkers/metabolism Blotting, Western Cell Differentiation Cells, Cultured Enhancer of Zeste Homolog 2 Protein Histone-Lysine N-Methyltransferase/metabolism Histones/metabolism Immunohistochemistry Lysine/metabolism Methylation Mice Microscopy, Confocal Microscopy, Fluorescence Polycomb Repressive Complex 2 Retina/embryology,metabolism Retinal Ganglion Cells/metabolism
Chemicals
Biomarkers Histones Enhancer of Zeste Homolog 2 Protein Ezh2 protein, mouse G9a protein, mouse Histone-Lysine N-Methyltransferase Polycomb Repressive Complex 2 Lysine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rao Rajesh C
Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Tchedre Kissaou T
Malik Muhammad Taimur A
Coleman Natasha
Fang Yuan
Marquez Victor E
Chen Dong Feng
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Article Info
Journal
Investigative ophthalmology & visual science
Abbr.
Invest Ophthalmol Vis Sci
ISSN
1552-5783
DOI
10.1167/iovs.09-4730
Published
2010-12-00
Epub
2010-00-29
Pages
6784-92
Language
English
Region
United States
NLM ID
7703701
PMCID
PMC3055777
Subset
IM
Grants
NEI NIH HHS · R01EY017641 · United States
RRD VA · I01 RX000110 · United States
NIDA NIH HHS · R21DA024803 · United States
NIDA NIH HHS · R21 DA024803 · United States
NEI NIH HHS · P30EY003790 · United States
Intramural NIH HHS · United States
NEI NIH HHS · P30 EY003790 · United States
NEI NIH HHS · R01 EY017641 · United States
External Links
PubMed source DOI: 10.1167/iovs.09-4730 PMC Full Text View journal details
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