A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron.
A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron.
复制标题
ZFP281-AFF3 在控制印记 Meg3 多顺反子方面调节的允许染色质状态。
DOI：
10.1093/nar/gkw1051
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发表时间：
2017-02-17
影响因子：
14.9
通讯作者：
Lin C
中科院分区：
文献类型：
--
作者：
Wang Y;Shen Y;Dai Q;Yang Q;Zhang Y;Wang X;Xie W;Luo Z;Lin C
基因组印记是一种表观遗传调控，它导致基因以亲本起源的特定方式表达。AFF3是超延长复合体3(SEC-L3)的中心成分，在印记的Dlk1-dio3基因座的基因间差异甲基化区域(IG-DMR)和Meg3增强子上都富含AFF3，以调控该基因座的等位基因特异性表达。AFF3到IG-DMR的本地化需要ZFP 57。然而，AFF3在Meg3增强子中如何维持等位基因特异性表达仍不清楚。在这里，我们证明AFF3与Krüppel样锌指蛋白ZFP281在小鼠胚胎干细胞中相关。ZFP281将AFF3招募到印记的Dlk1-dio3基因座中的Meg3增强子，从而调节Meg3多顺反子的等位基因特异性表达。我们的全基因组分析进一步确认ZFP281是一个关键因子，通常与AFF3在增强子上相关，并与AFF3一起调节一组基因的表达。我们的研究表明，不同的锌指蛋白可以将AFF3招募到不同的调控元件上，并以上下文依赖的方式对AFF3的功能进行差异调节。
Genomic imprinting is an epigenetic regulation that leads to gene expression in a parent-of-origin specific manner. AFF3, the central component of the Super Elongation Complex-like 3 (SEC-L3), is enriched at both the intergenic-differentially methylated region (IG-DMR) and the Meg3 enhancer within the imprinted Dlk1-Dio3 locus to regulate the allele-specific gene expression in this locus. The localization of AFF3 to IG-DMR requires ZFP57. However, how AFF3 functions at the Meg3 enhancer in maintaining allele-specific gene expression remains unclear. Here, we demonstrate that AFF3 is associated with the Krüppel-like zinc finger protein ZFP281 in mouse embryonic stem (ES) cells. ZFP281 recruits AFF3 to the Meg3 enhancer within the imprinted Dlk1-Dio3 locus, thus regulating the allele-specific expression of the Meg3 polycistron. Our genome-wide analyses further identify ZFP281 as a critical factor generally associating with AFF3 at enhancers and functioning together with AFF3 in regulating the expression of a subset of genes. Our study suggests that different zinc finger proteins can recruit AFF3 to different regulatory elements and differentially regulate the function of AFF3 in a context-dependent manner.