A permissive chromatin state regulated by ZFP281-AFF3 in controlling the imprinted Meg3 polycistron.
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.
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Yan
Y
Wang
Bioinformatics Core, A*STAR Genome Institute of Singapore, 60 Biopolis Street, Singapore.
Yang
Y
Shen
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Qian
Q
Dai
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Qian
Q
Yang
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Yue
Y
Zhang
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Xin
X
Wang
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Wei
W
Xie
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Zhuojuan
Z
Luo
Institute of Life Sciences, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China.
Chengqi
C
Lin
D000818:Animals; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D018392:Genomic Imprinting; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007453:Iodide Peroxidase / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D002843:Chromatin; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C484354:Laf4 protein, mouse; C422882:MEG3 non-coding RNA, mouse; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; C540267:Zfp281 protein, mouse; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase