Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation.
Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation.
复制标题
Pygo2 通过促进组蛋白 H3 K4 甲基化来扩增乳腺祖细胞
DOI：
10.1083/jcb.200810133
复制
发表时间：
2009-06-01
期刊：
影响因子：
--
通讯作者：
Dai X
中科院分区：
文献类型：
--
作者：
Gu B;Sun P;Yuan Y;Moraes RC;Li A;Teng A;Agrawal A;Rhéaume C;Bilanchone V;Veltmaat JM;Takemaru K;Millar S;Lee EY;Lewis MT;Li B;Dai X
最近的研究明确地发现了乳腺中的多潜能干/祖细胞，为揭示上皮干/祖细胞发育和动态平衡的遗传和表观遗传调控提供了一个易操作的模型系统。在本研究中，我们发现在胚胎和出生后的乳房祖细胞中表达的PYGO-2，是进化保守的植物同源结构域蛋白家族的成员。PYGO-2缺乏症是通过完全或上皮特异性基因去除在小鼠身上实现的，导致乳腺形态发生和再生缺陷，伴随着严重损害上皮祖细胞的扩张性自我更新。PYGO-2与Wnt/β-catenin信号在祖细胞调控和细胞周期基因表达上趋同，PYGO-2的缺失完全挽救了β-catenin诱导的乳腺生长。我们进一步描述了PYGO-2的一个新的分子功能，它是通过直接与K4-甲基组蛋白H3结合和募集组蛋白H3-K4甲基转移酶复合体，促进组蛋白H3的K4三甲基化，无论是在全局上还是在Wnt/β-Catenin靶基因上。
Recent studies have unequivocally identified multipotent stem/progenitor cells in mammary glands, offering a tractable model system to unravel genetic and epigenetic regulation of epithelial stem/progenitor cell development and homeostasis. In this study, we show that Pygo2, a member of an evolutionarily conserved family of plant homeo domain–containing proteins, is expressed in embryonic and postnatal mammary progenitor cells. Pygo2 deficiency, which is achieved by complete or epithelia-specific gene ablation in mice, results in defective mammary morphogenesis and regeneration accompanied by severely compromised expansive self-renewal of epithelial progenitor cells. Pygo2 converges with Wnt/β-catenin signaling on progenitor cell regulation and cell cycle gene expression, and loss of epithelial Pygo2 completely rescues β-catenin–induced mammary outgrowth. We further describe a novel molecular function of Pygo2 that is required for mammary progenitor cell expansion, which is to facilitate K4 trimethylation of histone H3, both globally and at Wnt/β-catenin target loci, via direct binding to K4-methyl histone H3 and recruiting histone H3 K4 methyltransferase complexes.
登录
查看更多内容
影响因子：
4.8
作者：
Filali, M;Cheng, NL;Engelhardt, JF
通讯作者：
Engelhardt, JF
影响因子：
4.8
作者：
Chen, CF;Chen, PL;Lee, WH
通讯作者：
Lee, WH
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
影响因子：
23.9
作者：
Cui K;Zang C;Roh TY;Schones DE;Childs RW;Peng W;Zhao K
通讯作者：
Zhao K
影响因子：
56.9
作者：
Cheng, T;Rodrigues, N;Scadden, DT
通讯作者：
Scadden, DT