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Evgenya Popova, Samuel Shao-Min Zhang, Xuming Xu, Andrew DeWan, Josephine Hoh, Colin J. Barnstable; Stage and Gene Specific Signatures of H3K4me2 and H3K27me3 Accompany Mammalian Retina Maturation in vivo. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3946.
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© ARVO (1962-2015); The Authors (2016-present)
Histone modifications are sensitive indicators, and possibly predictors, of gene expression in developing tissues, but the complexity of the epigenetic code is far from understood. In this study we have followed the distribution of H3K4me2 and H3K27me3 over the whole genome during mouse retina development and have related modification patterns to specific classes of genes.
Animal use was in accordance with ARVO/IACUC guidelines. Immunocytochemistry and biochemical studies were conducted with eyes collected from C57BL/6j mice (Jackson Laboratory) at 4 developmental stages from E17 to PN15. ChIP-Seq analysis of retinal chromatin was performed with antibodies against H3K4me2 and H3K27me3. ChIP DNA was sequenced on the Illumina Genome Analyzer. Data were analyzed with in-house program and NexGENe software.
When visualized by immunocytochemistry H3K4me2 and H3K27me3 each showed changing cellular patterns of distribution during retina development and a markedly different localization in the nuclei of rod photoreceptor cells. ChIP-Seq analysis of H3K4me2 and H3K27me3 accumulation around the Transcription Start Site (TSS) of genes uniquely expressed in rod photoreceptors showed a dramatic de-novo increase of H3K4me2 around TSS after PN7 but complete absence of H3K27me3 on the same genes throughout development. Other genes upregulated in retina during development show a similar increase of H3K4me2 developmental accumulation at their TSS but a dramatic decrease in H3K27me3 during terminal differentiation. In addition to the specific patterns around the TSS, H3K4me2 and H3K27me3 have gene specific distribution over the whole gene body of tissue specific genes. Rod specific genes accumulate H3K4me2, but not H3K27me3 over the whole gene whereas genes expressed in the retina non-rod cells show extensive H3K27me3 accumulation over the gene in the mature retina.
We have identified unique epigenetic developmental signatures of H3K4me2 and H3K27me3 around the TSS and on gene bodies that can distinguish cell type specific genes from genes expressed more widely. By comparing these signatures for different types of genes with measured levels of expression, we propose that different strategies are used to regulate chromatin structure around different types of genes during development.
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