鉴定 Meg3 差异甲基化区域的印迹调控因子。
Identification of imprinting regulators at the Meg3 differentially methylated region.
机构信息
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA.
出版信息
Genomics. 2012 Sep;100(3):184-94. doi: 10.1016/j.ygeno.2012.06.001. Epub 2012 Jun 15.
Abstract
Genomic imprinting at the Delta-like 1 (Dlk1)-Maternally expressed gene 3 (Meg3) locus is regulated by the Meg3 differentially methylated region (DMR), but the mechanism by which this DMR acts is unknown. The goal of this study was to analyze the Meg3 DMR during imprinting establishment and maintenance for the presence of histone modifications and trans-acting DNA binding proteins using chromatin immunoprecipitation. In embryonic stem (ES) cells, where Meg3 is biallelically expressed, the DMR showed variable DNA methylation, with biallelic methylation at one region but paternal allele-specific methylation at another. All histone modifications detected at the Meg3 DMR of ES cells were biallelic. In embryonic day 12.5 (e12.5) embryos, where Meg3 is maternally expressed, the paternal Meg3 DMR was methylated, and activating histone modifications were specific to the maternal DMR. DNA-binding proteins that represent potential regulatory factors were identified in both ES cells and embryos.
摘要
基因组印迹在 Delta-like 1 (Dlk1) - 母系表达基因 3 (Meg3) 基因座受 Meg3 差异甲基化区域 (DMR) 调控，但该 DMR 的作用机制尚不清楚。本研究的目的是使用染色质免疫沉淀技术分析印迹建立和维持过程中 Meg3 DMR 中组蛋白修饰和反式作用 DNA 结合蛋白的存在。在胚胎干细胞 (ES) 中，Meg3 呈双等位基因表达，DMR 显示出可变的 DNA 甲基化，一个区域呈双等位基因甲基化，另一个区域呈父本等位基因特异性甲基化。在 ES 细胞中检测到的所有 Meg3 DMR 组蛋白修饰均呈双等位基因。在母系表达 Meg3 的胚胎第 12.5 天 (e12.5) 胚胎中，父本 Meg3 DMR 甲基化，激活组蛋白修饰特异性位于母本 DMR。在 ES 细胞和胚胎中均鉴定到代表潜在调节因子的 DNA 结合蛋白。
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