Somatic XIST activation and features of X chromosome inactivation in male human cancers.

IF 9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Systems Pub Date : 2022-11-16 DOI:10.1016/j.cels.2022.10.002
Ananthan Sadagopan, Imran T Nasim, Jiao Li, Mingkee Achom, Cheng-Zhong Zhang, Srinivas R Viswanathan
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引用次数: 5

Abstract

Expression of the non-coding RNA XIST is essential for initiating X chromosome inactivation (XCI) during early development in female mammals. As the main function of XCI is to enable dosage compensation of chromosome X genes between the sexes, XCI and XIST expression are generally absent in male normal tissues, except in germ cells and in individuals with supernumerary X chromosomes. Via a systematic analysis of public sequencing data of both cancerous and normal tissues, we report that XIST is somatically activated in a subset of male human cancers across diverse lineages. Some of these cancers display hallmarks of XCI, including silencing of gene expression, reduced chromatin accessibility, and increased DNA methylation across chromosome X, suggesting that the developmentally restricted, female-specific program of XCI can be somatically accessed in male cancers.

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男性癌症患者的体细胞XIST激活及X染色体失活特征。
非编码RNA XIST的表达是雌性哺乳动物早期发育过程中启动X染色体失活(XCI)的必要条件。由于XCI的主要功能是使X染色体基因在两性之间进行剂量补偿,所以除了生殖细胞和有多余X染色体的个体外,XCI和XIST在男性正常组织中一般不表达。通过对癌组织和正常组织的公开测序数据的系统分析,我们报告了XIST在不同谱系的男性癌症的一个子集中被体细胞激活。其中一些癌症表现出XCI的特征,包括基因表达沉默、染色质可及性降低和X染色体DNA甲基化增加,这表明发育受限的女性特异性XCI程序可以在男性癌症中获得。
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来源期刊
Cell Systems
Cell Systems Medicine-Pathology and Forensic Medicine
CiteScore
16.50
自引率
1.10%
发文量
84
审稿时长
42 days
期刊介绍: In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.
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