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[剂量补偿与MSL复合体的研究进展]

[Research advance of dosage compensation and MSL complex].

作者信息

Sun Min-Qiu, Lin Peng, Chen Yun, Wang Yi-Lei, Zhang Zi-Ping

机构信息

Fisheries College, Jimei University, Xiamen 361021, China.

出版信息

Yi Chuan. 2012 May;34(5):533-44. doi: 10.3724/sp.j.1005.2012.00533.

DOI:10.3724/sp.j.1005.2012.00533
PMID:22659425
Abstract

Dosage compensation effect, which exists widely in eukaryotes with sexual reproduction, is an essential biological process that equalizes the level of gene expression between genders based on sex determination. In Drosophila, the male-specific lethal (MSL) complex mediates dosage compensation by acetylating histone H4 lysine K16 on nucleosome of some specific sites on the male X chromosome, globally upregulates twofold expression of active X-linked genes from the single X chromosome, and makes up for the shortage that the male has only one single X chromosome in male Drosophila. Up to date, the structure of basic components of MSL complex, which consists of at least five protein subunits and two non-coding RNAs, has already been revealed, and the interaction sites among these components have also been generally identified. Furthermore, abundant researches on recognition mechanism of the complex have been published. In contrast, many studies have revealed that mammalian dosage compensation functions by silencing gene expression from one of the two X chromosomes in females. The main components of mammalian MSL complex have already been identified, but the knowledge of their function is limited. Up to now, research of MSLs in teleosts is scarcely studied. This review summarizes the similarities and differences among dosage compensation mechanisms of nematodes, fruit flies and mammals, introduces the recent research advances in MSL complex, as well as molecular mechanism of dosage compensation in fruit fly, and finally addresses some problems to be resolved. Meanwhile, the diversity of msl3 gene in fishes is found by synteny analysis. This information might provide insightful directions for future research on the mechanisms of dosage compensation in various species.

摘要

剂量补偿效应广泛存在于进行有性生殖的真核生物中,是一种重要的生物学过程,它基于性别决定使两性之间的基因表达水平达到均衡。在果蝇中,雄性特异性致死(MSL)复合物通过乙酰化雄性X染色体上某些特定位点核小体上的组蛋白H4赖氨酸K16来介导剂量补偿,使来自单条X染色体的活性X连锁基因的表达整体上调两倍,并弥补雄性果蝇只有一条X染色体的不足。到目前为止,已经揭示了由至少五个蛋白质亚基和两个非编码RNA组成的MSL复合物基本成分的结构,并且这些成分之间的相互作用位点也已基本确定。此外,关于该复合物识别机制的大量研究已经发表。相比之下,许多研究表明哺乳动物的剂量补偿是通过使雌性两条X染色体之一的基因表达沉默来实现的。哺乳动物MSL复合物的主要成分已经确定,但其功能的相关知识有限。到目前为止,硬骨鱼中MSL的研究几乎没有。这篇综述总结了线虫、果蝇和哺乳动物剂量补偿机制之间的异同,介绍了MSL复合物的最新研究进展以及果蝇剂量补偿的分子机制,最后提出了一些有待解决的问题。同时,通过共线性分析发现了鱼类中msl3基因的多样性。这些信息可能为未来各种物种剂量补偿机制的研究提供有见地的方向。

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1
[Research advance of dosage compensation and MSL complex].[剂量补偿与MSL复合体的研究进展]
Yi Chuan. 2012 May;34(5):533-44. doi: 10.3724/sp.j.1005.2012.00533.
2
A new strategy for isolating genes controlling dosage compensation in Drosophila using a simple epigenetic mosaic eye phenotype.利用简单的表观遗传镶嵌眼表型分离控制果蝇剂量补偿的基因的新策略。
BMC Biol. 2010 Jun 10;8:80. doi: 10.1186/1741-7007-8-80.
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The right dose for every sex.适合每种性别的正确剂量。
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4
Non-coding roX RNAs prevent the binding of the MSL-complex to heterochromatic regions.非编码roX RNA可阻止MSL复合物与异染色质区域结合。
PLoS Genet. 2014 Dec 11;10(12):e1004865. doi: 10.1371/journal.pgen.1004865. eCollection 2014 Dec.
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MSL proteins and the regulation of gene expression.MSL蛋白与基因表达调控
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MOF-regulated acetylation of MSL-3 in the Drosophila dosage compensation complex.MOF调控果蝇剂量补偿复合物中MSL-3的乙酰化作用。
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Targeting of MOF, a putative histone acetyl transferase, to the X chromosome of Drosophila melanogaster.将假定的组蛋白乙酰转移酶MOF靶向黑腹果蝇的X染色体。
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8
The roX genes encode redundant male-specific lethal transcripts required for targeting of the MSL complex.roX基因编码MSL复合体靶向所需的冗余雄性特异性致死转录本。
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The essential Drosophila CLAMP protein differentially regulates non-coding roX RNAs in male and females.果蝇中至关重要的CLAMP蛋白对雄性和雌性中的非编码roX RNA进行差异性调控。
Chromosome Res. 2017 Jun;25(2):101-113. doi: 10.1007/s10577-016-9541-9. Epub 2016 Dec 19.
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The non-dosage compensated Lsp1alpha gene of Drosophila melanogaster escapes acetylation by MOF in larval fat body nuclei, but is flanked by two dosage compensated genes.果蝇的非剂量补偿Lsp1alpha基因在幼虫脂肪体细胞核中逃避了MOF介导的乙酰化作用,但它两侧有两个剂量补偿基因。
BMC Mol Biol. 2007 May 19;8:35. doi: 10.1186/1471-2199-8-35.