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Hyun-Jin Yang, Jung-Woong Kim, Vijender Chaitankar, Matthew Brooks, Hong Hao, Anand Swaroop; Integrated transcriptome and epigenome analysis of developing mouse rod photoreceptors reveals dynamic epigenetic control of lineage priming and developmental plasticity. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):437.
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© ARVO (1962-2015); The Authors (2016-present)
Functional maturation of rod photoreceptors takes place over an extended period of time and is associated with extensive changes in gene expression patterns. Despite a well-established role of NRL in controlling vast majority of rod genes, how precise temporal gene expression is established remains poorly understood. To explore the possible contribution of epigenetic factors in temporal regulation of rod gene expression, we have undertaken integrated transcriptome and epigenome analysis of developing and mature mouse rod photoreceptors.
We isolated rod photoreceptors from Nrlp-GFP mouse retina at various developmental stages and generated rod-specific transcriptome, NRL targetome and epigenome profiles.
Epigenetic architecture of newly post-mitotic rods was highly favorable for expression of cone genes but not of rod genes, while rod-photoreceptor specific epigenetic signature was fully established by adult stage. This change is consistent with transient cone gene expression detected in most immature rods and late onset of many rod genes. Notably, NRL recruitment to target genes was also delayed despite a constantly high level of Nrl expression throughout rod development. Our epigenome data also revealed genes specific for non-photoreceptor retinal neurons bearing both active and repressive epigenetic marks in immature rods, constituting a novel class of genes with bivalent chromatin marks. This bivalency was lost in mature rods.
We conclude that immature rods remain epigenetically plastic with their chromatin state primed for S-cone fate, consistent with our recent finding that most mouse rods are recruited from S cone lineage. Bivalent chromatin state identified in non-photoreceptor retinal genes likely reflects the developmental history transiently retained in newly post-mitotic rods as rods are one of the late born neurons from common pools of retinal progenitor cells. A subsequent massive reorganization of chromatin state takes place as rods mature, thereby allowing regulation of rod gene expression in a timely manner.
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