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E. Popova, A. DeWan, J. Hoh, S. S. Zhang, C. J. Barnstable; Heterochromatin Spreading and Epigenetic Changes at the Gene Promoters During Mouse Rod Photoreceptor Development. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5939.
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© ARVO (1962-2015); The Authors (2016-present)
Development of the mammalian retinal outer nuclear layer is characterized by progressive changes in chromatin structure and accumulation of heterochromatin inside rod cell nuclei. The goals of this study are to elucidate the epigenetic mechanisms regulating this process and the influence of chromatin condensation on gene transcription and also to define epigenetic changes at promoter regions during retina development.
Animal use was in accordance with ARVO / IACUC guidelines. Electron microscopy and biochemical studies were conducted with eyes collected from C57BL/6j mice (Jackson Laboratory) at 5 developmental stages from E17 to PN56. ChIP-Seq analysis of retinal chromatin was performed with antibodies against H3K4me2, H3K9me2 and H4K20me3. ChIP DNA was sequenced on the Illumina Genome Analyzer. Data were analyzed with NexGENe software.
We found that during mouse rod maturation: 1) Heterochromatin is accumulated in the center of the rod nuclei after PN15, so that in adult euchromatin forms only a peripheral ring in the nucleus. 2) Heterochromatization is accompanied by an increase in nucleosomal repeat length after PN15, an overall increase in amounts of linker histone H1 (with increased H1c and decreased H1o) and changes in histone modifications. 3) At E17, histone modification H3K4me2 marked promoters and the upstream regions mostly of housekeeping genes, while in the adult this mark was generally decreased and specifically eliminated from the promoter regions. 4) Epigenetic heterochromatin modifications H3K9me2 and H4K20me3 marked intergenic / introns regions, and some blocks of intergenic regions show dramatic increased in H3K9me2 mark in adult.
Heterochromatin condensation during terminal rod differentiation may be regulated by accumulation of linker histone H1c. This process is accompanied by epigenetic changes at promoter regions where a marker of euchromatin, H3K4me2, is eliminated and the changes in this histone modification appears to differentially affect housekeeping and cell-type specific genes.
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