JBC重点推荐厦大特聘教授文章 癌症靶位研究成果

　　

生物通报道，厦门大学生命科学院闽江学者特聘教授李博安在JBC（Journal of Cell Biology）上发表高水平文章Pygo2 expands mammary progenitor cells by facilitating histone H3K4 methylation。被JBC作为重要发现予以专评并做重点介绍。

 

李博安教授从事发育与肿瘤细胞生物学研究，主要研究领域为Wnt信号通路在正常组织发育和肿瘤形成中的作用。

 

Pygo2是β-catenin的结合蛋白，然而起在哺乳动物中的生物学功能和调节Wnt信号的分子机理仍然不清楚。

 

李博安教授课题组以基因敲出小鼠为模型进行研究，发现Pygo2基因敲出小鼠乳腺发育严重受损，Pygo2调节了乳腺胚胎期和成体干细胞/祖细胞的扩张性自我更新。Pygo2通过募集H3K4甲基化转移酶调节染色质的甲基化，使染色质处于激活状态；另一方面，其PHD结构又能够与H3K4Me3染色质标记结合，增强转录因子复合体的稳定性，同时行驶表观调控和启动特异性基因转录的作用。

 

这一发现表明，阻断Pygo2的功能可以作为一个潜在的治疗靶点，抑制乳腺细胞的过度增生和Wnt信号的过渡激活，为乳腺癌的治疗奠定基础。

（生物通 小茜）

生物通推荐原文检索：Pygo2 expands mammary progenitor cells by facilitating histone H3K4 methylation

【Abstract】

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.