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Samir S. Deeb, Darren Bisset, Samin Sajan, Jo Ling Liao, R. David Hawkins; Regulation of Photoreceptor Gene Expression by Thyroid Hormone Involves Alterations in Histone Methylation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5131.
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We previously showed that thyroid hormone (T3) induces or represses expression of genes in the human cone-like retinoblastoma cell line WERI-Rb1. Histone lysine modifications (HKM) are correlated with chromatin architecture and play key roles in photoreceptor differentiation during retinal development. The purpose of this study was to assign enhancers to promoters by correlating changes in gene expression by T3 with genomic changes in HKM.
WERI cells were grown in the absence or presence of T3. Chromatin-immunoprecipitation analysis was performed to map genomic sites that are associated with histone 3-lysine 4-monomethylation (H3K4me1, associated with active enhancers), or trimethylation sites (H3K4me3, associated with active promoters). These HKM marks were compared with gene expression.
Significant alteration in the positions and levels of H3K4me1 and H3K4me3 marks were observed at genes that are induced or repressed by T3. The promoters and potential enhancers of most genes that are induced by T3, including those that encode the red and green opsin genes, showed an increase in binding of H3K4me1 and H3K4me3, respectively. In contrast, genes that are repressed by T3 generally showed the opposite results. A few of the genes induced or repressed by T3 had no significant changes in the levels of the above types of methylated histones bound to enhancers or promoters.
Regulation of gene expression in WERI cells by T3 includes alterations in the levels of histone lysine methylation, suggesting that this process also contributes to the control of gene expression by T3 during cone photoreceptor development.
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