近些年來，干細胞的研究為未來醫(yī)學帶來了很大希望,，但是干細胞也可能是引發(fā)某些疾病的原因,。當自我更新、非特化的細胞不能夠分化成為多種類型的成熟細胞時,，干細胞就會分裂失控,，引發(fā)癌癥。近日,，來自魏茲曼研究所的研究人員首次揭示了癌癥和干細胞錯誤分化之間的關系,，相關研究成果刊登在了近日的國際雜志Molecular Cell上。
研究者設法解開干細胞分化過程中DNA改裝過程的詳細過程,，結果顯示,，對于干細胞的合適分化來說，特定的DNA包裝必須被泛素進行標記,，這樣的標記為開啟一系列的基因表達必不可少,，這會促使干細胞進行分化。研究人員發(fā)現(xiàn)了兩個開關,，酶RNF20可以增強標記功能,，另外一種酶USP44，功能恰恰相反，關閉這種標簽功能,。此外,，這些開關必須合適地工作以保證分化過程有效的進行。當干擾這些標記時,，干細胞便失去分化的能力,。
實驗結果揭示了在很多癌癥中識別的分子缺陷，比如在特定乳腺癌和前列腺癌中發(fā)現(xiàn)的異常的低水平RNF20等,。值得注意的是,，干細胞的錯誤分化通常是癌癥發(fā)生惡性轉變的標志。
這項研究屬于癌癥研究最新的方向,，除了重點研究基因的功能外,，研究者還強調研究了實驗胚胎學的重要性，對其進行研究并不會修飾基因的模式,，但是會影響其信息路徑。理解癌癥的表觀遺傳學根源對于開發(fā)出新型治療方法至關重要,。（生物谷Bioon.com）
編譯自：Judging DNA by Its Cover: Explaining the Link Between Stem Cells and Cancer
doi:10.1016/j.molcel.2012.05.023
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RNF20 and USP44 Regulate Stem Cell Differentiation by Modulating H2B Monoubiquitylation
Gilad Fuchs, Efrat Shema, Rita Vesterman, Eran Kotler, Zohar Wolchinsky, Sylvia Wilder, Lior Golomb, Ariel Pribluda, Feng Zhang, Mahmood Haj-Yahya, Ester Feldmesser, Ashraf Brik, Xiaochun Yu, Jacob Hanna, Daniel Aberdam, Eytan Domany, Moshe Oren
Embryonic stem cells (ESCs) maintain high genomic plasticity, which is essential for their capacity to enter diverse differentiation pathways. Posttranscriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner.
