Epigenetic control of expression of the human L- and M- pigment genes
Epigenetic control of expression of the human L- and M- pigment genes
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DOI：
10.1111/j.1475-1313.2010.00735.x
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发表时间：
2010-09-01
影响因子：
2.9
通讯作者：
Fu, L.
中科院分区：
文献类型：
--
作者：
Deeb, S. S.;Bisset, D.;Fu, L.
表观遗传学通过染色质修饰来改变基因表达，而不改变 DNA 序列。 DNA甲基化是表观遗传基因调控的重要信号。 DNA 中 CpG 二核苷酸的胞嘧啶碱基甲基化会导致染色质浓缩，从而抑制基因表达。 DNA 甲基化已被证明在细胞分化、基因组印记和 X 染色体失活中发挥重要作用。我们比较了 L-视蛋白基因 (OPN1LW) 和 M-视蛋白基因 (OPN1MW) 启动子的 CpG 甲基化模式，以及位于 OPN1LW 基因上游约 8 kb（千碱基）的 DNase I 超敏感 (DHS) 位点。使用人视网膜母细胞瘤细胞系 WERI 和不表达这些基因的淋巴母细胞系 GM06990 进行比较。WERI 在用甲状腺激素 (T3) 处理时表达 L 和 M 视蛋白基因。结果显示，位于每个启动子近端 200 bp（碱基对）以及 5'-非翻译区的 20 bp 内的 14 个 CpG 中的绝大多数是无论是否用 T3 处理，WERI-Rb-1 细胞中的甲基化程度较低，但在类淋巴母细胞系中几乎完全甲基化。距离 OPN1LW 转录起始位点超过 200 bp 的三个 CpG 在 WERI 和类淋巴母细胞中均高度甲基化。在 DHS 区域（24 个 CpG）内也观察到显着差异的甲基化。该 DHS 区域包含一个高度保守的基序，可结合 CCCTC 结合因子 (CTCF)，称为“染色质绝缘体或边界元件”，已被证明可以调节多个基因组位置的基因表达。结果表明，DNA 甲基化可能有助于调节分化过程中 L- 和 M- 视蛋白基因的表达，以及视网膜 L:M 锥体比率。此外，甲状腺激素对视蛋白基因的诱导似乎不会改变 DNA 甲基化。
Epigenetics alters gene expression by chromatin modification without changing the sequence of DNA. DNA methylation is an essential signal for epigenetic gene regulation. Methylation of cytosine bases at CpG dinucleotides in DNA results in chromatin condensation resulting in suppression of gene expression. DNA methylation has been shown to play important roles in cell differentiation, genomic imprinting and X-chromosome inactivation. We compared the CpG methylation patterns of the promoters of the L-opsin gene (OPN1LW) and the M-opsin gene (OPN1MW), plus a DNase I hypersensitive (DHS) site located about 8 kb (kilobases) upstream of the OPN1LW gene. Comparisons were made using the human retinoblastoma cell line WERI, which expresses the L and M opsin genes when treated with thyroid hormone (T3), and a lymphoblastoid cell line GM06990 that does not express these genes.The results showed that the great majority of the 14 CpGs located within the proximal 200 bp (base pairs) of each promoter, plus 20 bp of the 5'-untranslated region, were hypo-methylated in WERI-Rb-1 cells, whether or not treated with T3, but almost totally methylated in the lymphoblastoid cell line. Three of the CpGs that are located beyond 200 bp from the transcription start site of OPN1LW were hyper-methylated in both WERI and lymphoblastoid cells. Significant differential methylation was also observed within the DHS region (24 CpGs). This DHS region contains a highly conserved motif that binds CCCTC-binding factor (CTCF), referred to as a 'chromatin insulator or boundary element', that has been shown to regulate gene expression at several genome locations. The results suggest that DNA methylation is likely to contribute to regulation of expression of the L- and M-opsin genes during differentiation, as well as to the retinal L:M cone ratio. In addition, thyroid hormone induction of the opsin genes does not appear to alter DNA methylation.