Smek promotes histone deacetylation to suppress transcription of Wnt target gene brachyury in pluripotent embryonic stem cells  

作　　者：Jungmook Lyu Eek-hoon Jho Wange Lu 

机构地区：[1]The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA [2]Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA [3]Department of Life Science, University of Seoul, Seoul 130- 743, Korea

出　　处：《Cell Research》2011年第6期911-921,共11页细胞研究（英文版）

摘　　要：In embryonic stem cells （ESCs）, Wnt-responsive development-related genes are silenced to maintain pluripotency and their expression is activated during differentiation. Acetylation of histones by histone acetyltransferases stimulates transcription, whereas deacetylation of histones by HDACs is correlated with transcriptional repression. Although Wnt-mediated gene transcription has been intimately linked to the acetylation or deacetylation of histones, how Wnt signaling regulates this type of histone modification is poorly understood. Here, we report that Smek, a reg- ulatory subunit of protein phosphatase 4 （PP4） complex, plays an important role in histone deacetylation and silenc- ing of the Wnt-responsive gene, brachyury, in ESCs. Smek mediates recruitment of PP4c and HDAC1 to the Tcf/Lef binding site of the brachyury promoter and inhibits brachyury expression in ESCs. Activation of Wnt signaling during differentiation causes disruption of the Smek/PP4c/HDAC1 complex, resulting in an increase in histones H3 and H4 acetylation at the brachyury gene locus. These results suggest that the Smek-containing PP4 complex represses transcription of Wnt-responsive development-related genes through histone deacetylation, and that this complex is essential for ESC pluripotency maintenance.

关 键 词：embryonic stem cell Smek HDAC 1 protein phosphatase 4 complex Wnt signaling differentiation 

分 类 号：Q512.7[生物学—生物化学] Q2