哈佛醫(yī)學院,，波士頓兒童醫(yī)院Dana-Farber癌癥研究所,，霍華休斯醫(yī)學研究所,，麻省總醫(yī)院以及威斯康辛大學醫(yī)學與公共衛(wèi)生學院的科學家在干細胞研究方面取得最新的進展，相關成果文章Jumonji Modulates Polycomb Activity and Self-Renewal versus Differentiation of Stem Cells公布在最新一期的Cell雜志上,。
文章的通訊作者是哈佛醫(yī)學院,，霍華休斯醫(yī)學院的Stuart H. Orkin教授，美國科學院院士,，他主要從事干細胞方面的研究,，尤其是造血系統(tǒng)的干細胞，以及癌癥與干細胞間的關系,。
組蛋白H3賴氨酸27（histone H3 lysine 27,，H3K27me3）甲基化必須在PRC2抑制復合物的作用下才能完成，H3K27me3對胚胎干細胞的自我更新和分化具有重要的調控作用,。
Polycomb group (PcG) 蛋白是一組通過染色質修飾調控靶基因的轉錄抑制子, 從生化和功能上它可以分成兩個主要的核心蛋白復合體PRC1(Polycomb repressive complex 1)和PRC2(Polycomb repressive complex 2),。研究發(fā)現PcG蛋白不僅控制個體正確的發(fā)育模式, 而且與細胞的增殖、分化和腫瘤發(fā)生有關,。
然而,，關于PRC2的作用機制卻不明確。在這篇文章中Stuart H. Orkin研究小組發(fā)現Jumonji家族成員，JMJ（JUMONJI或JARID2）與PRC2的功能相關,，與PRC2和H3K27me3共定位在染色質上,，并具有調整PRC2的功能。
在體外實驗中,，Stuart H. Orkin研究小組發(fā)現,，JMJ抑制PRC2甲基化酶的活性，同時增強胚胎干細胞H3K27me3在PRC2靶位上的標記,。JMJ對PRC2的功能具有重要的調節(jié)作用,。
這些研究成果表明，JMJ動態(tài)地調節(jié)PRC2的功能,，以此來維持胚胎干細胞自我更新與分化間的平衡,，一旦JMJ出現異常，可能導致胚胎干細胞自我更新于分化間的平衡被打破,，影響胚胎干細胞的正常功能的維持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, 24 December 2009 doi:10.1016/j.cell.2009.12.003
Jumonji Modulates Polycomb Activity and Self-Renewal versus Differentiation of Stem Cells
Xiaohua Shen1, Woojin Kim1, Yuko Fujiwara1, Matthew D. Simon5, Yingchun Liu4, Matthew R. Mysliwiec6, Guo-Cheng Yuan4, Youngsook Lee6 and Stuart H. Orkin1, 2, 3, ,
1 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA
2 Howard Hughes Medical Institute, Boston, MA 02115, USA
3 Harvard Stem Cell Institute, Boston, MA 02115, USA
4 Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, and Harvard School of Public Health, Boston, MA 02115, USA
5 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
6 Department of Anatomy, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA
Trimethylation on histone H3 lysine 27 (H3K27me3) by Polycomb repressive complex 2 (PRC2) regulates the balance between self-renewal and differentiation of embryonic stem cells (ESCs). The mechanisms controlling the activity and recruitment of PRC2 are largely unknown. Here we demonstrate that the founding member of the Jumonji family, JMJ (JUMONJI or JARID2), is associated with PRC2, colocalizes with PRC2 and H3K27me3 on chromatin, and modulates PRC2 function. In vitro JMJ inhibits PRC2 methyltransferase activity, consistent with increased H3K27me3 marks at PRC2 targets in Jmj-/- ESCs. Paradoxically, JMJ is required for efficient binding of PRC2, indicating that the interplay of PRC2 and JMJ fine-tunes deposition of the H3K27me3 mark. During differentiation, activation of genes marked by H3K27me3 and lineage commitments are delayed in Jmj-/- ESCs. Our results demonstrate that dynamic regulation of Polycomb complex activity orchestrated by JMJ balances self-renewal and differentiation, highlighting the involvement of chromatin dynamics in cell-fate transitions.
