Tumor Suppressor Menin Represses Paired Box Gene 2 Expression via Wilms Tumor Suppressor Protein-Polycomb Group Complex

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	Tumor Suppressor Menin Represses Paired Box Gene 2 Expression via Wilms Tumor Suppressor Protein-Polycomb Group Complex
	Xu, Bin ; Zeng, De-quan ; Wu, Yuan ; Zheng, Rong ; Gu, Le ; Lin, Xiao ; Hua, Xianxin ; Jin, Guang-Hui ; Jin GH(金光辉)
刊名	http://dx.doi.org/10.1074/jbc.M110.197830
	2011-04-22
关键词	HISTONE METHYLTRANSFERASE COMPLEX KIDNEY DEVELOPMENT TARGET GENES ES CELLS WT1 CANCER GROWTH PAX-2 METHYLATION PROMOTER
英文摘要	National Natural Science Foundation of China [30701003, 81071926]; Natural Science Foundation of Xiamen [3502Z20104001]; fundamental research funds for the central universities [2010121106]; Tumor suppressor menin, the product of the MEN1 gene, plays a key role in controlling histone 3 lysine 4 trimethylation (H3K4me3) and gene transcription, which can regulate proliferation, apoptosis, and differentiation. However, little is known as to whether menin controls gene expression and cell proliferation and survival via regulating Polycomb group (PcG) protein complex/H3K27me3. Here we show that menin specifically represses transcription factor Paired box gene 2 (Pax2) through PcG-mediated H3K27me3 and Wilms tumor suppressor protein (WT1), a zinc finger domain-containing DNA-binding protein. Menin does not directly bind to the Pax2 locus, instead, it up-regulates WT1 expression. WT1 recruits PcG complex to the Pax2 promoter and represses expression of Pax2 through PcG-dependent H3K27me3. Moreover, WT1 also interacts with DNA methyltransferase 1 (DNMT1), and recruits DNMT1 to the Pax2 promoter, resulting in hypermethylation of CpG in the Pax2 promoter. Together, these studies have uncovered a novel epigenetic mechanism whereby menin regulates H3K27me3 and promoter DNA methylation via WT1 and suggest that WT1 protein plays an important, yet previously unappreciated role in regulating the function of the menin/PcG axis, H3K27 methylation, and DNA methylation, resulting in repression of gene transcription.
语种	英语
出版者	J BIOL CHEM
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93303]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Xu, Bin,Zeng, De-quan,Wu, Yuan,et al. Tumor Suppressor Menin Represses Paired Box Gene 2 Expression via Wilms Tumor Suppressor Protein-Polycomb Group Complex[J]. http://dx.doi.org/10.1074/jbc.M110.197830,2011.
APA	Xu, Bin.,Zeng, De-quan.,Wu, Yuan.,Zheng, Rong.,Gu, Le.,...&金光辉.(2011).Tumor Suppressor Menin Represses Paired Box Gene 2 Expression via Wilms Tumor Suppressor Protein-Polycomb Group Complex.http://dx.doi.org/10.1074/jbc.M110.197830.
MLA	Xu, Bin,et al."Tumor Suppressor Menin Represses Paired Box Gene 2 Expression via Wilms Tumor Suppressor Protein-Polycomb Group Complex".http://dx.doi.org/10.1074/jbc.M110.197830 (2011).