近些年來,，干細(xì)胞的研究為未來醫(yī)學(xué)帶來了很大希望，但是干細(xì)胞也可能是引發(fā)某些疾病的原因,。當(dāng)自我更新,、非特化的細(xì)胞不能夠分化成為多種類型的成熟細(xì)胞時(shí)，干細(xì)胞就會(huì)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(xì)胞錯(cuò)誤分化之間的關(guān)系,，相關(guān)研究成果刊登在了近日的國際雜志Molecular Cell上,。
研究者設(shè)法解開干細(xì)胞分化過程中DNA改裝過程的詳細(xì)過程，結(jié)果顯示,，對(duì)于干細(xì)胞的合適分化來說,，特定的DNA包裝必須被泛素進(jìn)行標(biāo)記，這樣的標(biāo)記為開啟一系列的基因表達(dá)必不可少,，這會(huì)促使干細(xì)胞進(jìn)行分化,。研究人員發(fā)現(xiàn)了兩個(gè)開關(guān)，酶RNF20可以增強(qiáng)標(biāo)記功能,，另外一種酶USP44,，功能恰恰相反，關(guān)閉這種標(biāo)簽功能,。此外,，這些開關(guān)必須合適地工作以保證分化過程有效的進(jìn)行。當(dāng)干擾這些標(biāo)記時(shí),，干細(xì)胞便失去分化的能力,。
實(shí)驗(yàn)結(jié)果揭示了在很多癌癥中識(shí)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(xì)胞的錯(cuò)誤分化通常是癌癥發(fā)生惡性轉(zhuǎn)變的標(biāo)志,。
這項(xiàng)研究屬于癌癥研究最新的方向,，除了重點(diǎn)研究基因的功能外，研究者還強(qiáng)調(diào)研究了實(shí)驗(yàn)胚胎學(xué)的重要性，對(duì)其進(jìn)行研究并不會(huì)修飾基因的模式,，但是會(huì)影響其信息路徑,。理解癌癥的表觀遺傳學(xué)根源對(duì)于開發(fā)出新型治療方法至關(guān)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.
