SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development.
SUMO-specific protease 2 (SENP2) has a broad de-SUMOylation activity in vitro. However, the biological function of SENP2 is largely unknown. Here, we show that deletion of SENP2 gene in mouse causes defects in the embryonic heart and reduces the expression of Gata4 and Gata6, which are essential for cardiac development. SENP2 regulates transcription of Gata4 and Gata6 mainly through alteration of occupancy of Pc2/CBX4, a polycomb repressive complex 1 (PRC1) subunit, on its promoters. We demonstrate that Pc2/CBX4 is a target of SENP2 in vivo and that SUMOylation is essential for Pc2/CBX4-mediated PRC1 recruitment to methylated histone 3 at K27 (H3K27me3). In SENP2 null embryos, SUMOylated Pc2/CBX4 accumulates and Pc2/CBX4 occupancy on the promoters of PcG target genes is markedly increased, leading to repression of Gata4 and Gata6 transcription. Our results reveal a critical role for de-SUMOylation in the regulation of PcG target gene expression.
Kang
Xunlei
X
The Department of Biochemistry and Molecular & Cell Biology, The Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qi
Yitao
Y
Zuo
Yong
Y
Wang
Qi
Q
Zou
Yanqiong
Y
Schwartz
Robert J
RJ
Cheng
Jinke
J
Yeh
Edward T H
ET
D000818:Animals; D003546:Cysteine Endopeptidases; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*
D009097:Multienzyme Complexes; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D003546:Cysteine Endopeptidases; C439066:Senp2 protein, mouse