A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron.

Yan Wang, Yang Shen, Qian Dai, Qian Yang, Yue Zhang, Xin Wang, Wei Xie, Zhuojuan Luo, Chengqi Lin

Nucleic acids research 2017 Feb 17

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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.

Citation

Yan Wang, Yang Shen, Qian Dai, Qian Yang, Yue Zhang, Xin Wang, Wei Xie, Zhuojuan Luo, Chengqi Lin. A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron. Nucleic acids research. 2017 Feb 17;45(3):1177-1185