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腾讯登录Mol Cell：揭示干细胞错误分化和癌症发生之间的关系
| 导读 | 近些年来，干细胞的研究为未来医学带来了很大希望，但是干细胞也可能是引发某些疾病的原因。当自我更新、非特化的细胞不能够分化成为多种类型的成熟细胞时，干细胞就会分裂失控，引发癌症。近日，来自魏兹曼研究所的研究人员首次揭示了癌症和干细胞错误分化之间的关系，相关研究成果刊登在了近日的国际杂志<em>Molecular Cell</em>上。
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近些年来，干细胞的研究为未来医学带来了很大希望，但是干细胞也可能是引发某些疾病的原因。当自我更新、非特化的细胞不能够分化成为多种类型的成熟细胞时，干细胞就会分裂失控，引发癌症。近日，来自魏兹曼研究所的研究人员首次揭示了癌症和干细胞错误分化之间的关系，相关研究成果刊登在了近日的国际杂志<em>Molecular Cell</em>上。
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研究者设法解开干细胞分化过程中DNA改装过程的详细过程，结果显示，对于干细胞的合适分化来说，特定的DNA包装必须被泛素进行标记，这样的标记为开启一系列的基因表达必不可少，这会促使干细胞进行分化。研究人员发现了两个开关，酶RNF20可以增强标记功能，另外一种酶USP44，功能恰恰相反，关闭这种标签功能。此外，这些开关必须合适地工作以保证分化过程有效的进行。当干扰这些标记时，干细胞便失去分化的能力。
实验结果揭示了在很多癌症中识别的分子缺陷，比如在特定乳腺癌和前列腺癌中发现的异常的低水平RNF20等。值得注意的是，干细胞的错误分化通常是癌症发生恶性转变的标志。
这项研究属于癌症研究最新的方向，除了重点研究基因的功能外，研究者还强调研究了实验胚胎学的重要性，对其进行研究并不会修饰基因的模式，但是会影响其信息路径。理解癌症的表观遗传学根源对于开发出新型治疗方法至关重要。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/07/120723105422.htm" target="_blank">Judging DNA by Its Cover: Explaining the Link Between Stem Cells and Cancer</a>
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<img src="http://www.bioon.com/biology/UploadFiles/201207/2012072501074686.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.1016/j.molcel.2012.05.023" target="_blank">doi:10.1016/j.molcel.2012.05.023</a>
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<br/><strong>RNF20 and USP44 Regulate Stem Cell Differentiation by Modulating H2B Monoubiquitylation</strong><br/>
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.
<br/>来源：生物谷
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研究者设法解开干细胞分化过程中DNA改装过程的详细过程，结果显示，对于干细胞的合适分化来说，特定的DNA包装必须被泛素进行标记，这样的标记为开启一系列的基因表达必不可少，这会促使干细胞进行分化。研究人员发现了两个开关，酶RNF20可以增强标记功能，另外一种酶USP44，功能恰恰相反，关闭这种标签功能。此外，这些开关必须合适地工作以保证分化过程有效的进行。当干扰这些标记时，干细胞便失去分化的能力。
实验结果揭示了在很多癌症中识别的分子缺陷，比如在特定乳腺癌和前列腺癌中发现的异常的低水平RNF20等。值得注意的是，干细胞的错误分化通常是癌症发生恶性转变的标志。
这项研究属于癌症研究最新的方向，除了重点研究基因的功能外，研究者还强调研究了实验胚胎学的重要性，对其进行研究并不会修饰基因的模式，但是会影响其信息路径。理解癌症的表观遗传学根源对于开发出新型治疗方法至关重要。
编译自：<a title="" href="http://www.sciencedaily.com/releases/2012/07/120723105422.htm" target="_blank">Judging DNA by Its Cover: Explaining the Link Between Stem Cells and Cancer</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201207/2012072501074686.jpg" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/doi:10.1016/j.molcel.2012.05.023" target="_blank">doi:10.1016/j.molcel.2012.05.023</a>
PMC:
PMID:
</div>
<div>
<br/><strong>RNF20 and USP44 Regulate Stem Cell Differentiation by Modulating H2B Monoubiquitylation</strong><br/>
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.
<br/>来源：生物谷
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