人类卫星II的染色质构造变化有助于瘤微环境中的衰老表型
Kenichi Miyata1,2,3, Xiangyu Zhou1, Mika Nishio1
1Division of Cellular Senescence, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
概括
细胞衰老触发了重复性DNA的变化,就像人类卫星II位点一样,促进了癌症的进展. 这些染色质变化增强炎症基因表达,有助于瘤生长.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 癌症研究 癌症研究
背景情况:
- 细胞衰老和瘤微环境 stromal 细胞中的衰老相关分泌表型 (SASP) 是已知的癌症进展的驱动因素.
- 细胞衰老会诱导高阶染色体结构变化和重复基因组元素的异常转录,但它们的功能意义仍然不清楚.
研究的目的:
- 研究细胞衰老期间重复元素中染色质结构变化的功能意义,重点研究人类卫星II (hSATII) 位点.
- 探索hSATII分解,改变色素可访问性,以及癌症中衰老和SASP相关基因的表达之间的联系.
主要方法:
- 在衰老诱导过程中检查人体卫星II (hSATII) 位点在周心区域.
- 乳腺癌组织的DNA-FISH分析,以评估hSATII分解.
- 重新分析单细胞ATAC-seq数据以将hSATII分解与基因表达相关联.
主要成果:
- 在衰老诱导过程中hSATII位点分解,在hSATIIRNA表达之前形成新的DNA-DNA相互作用 (DRISR).
- DRISR区域表现出改变的染色质可访问性,并为与衰老和炎症SASP基因相关的动机进行丰富.
- 在乳腺癌组织中,观察到hSATII分解在癌细胞和胸膜细胞中,与纤维细胞中SASP相关的基因表达增加相关.
结论:
- 在细胞衰老过程中,细胞衰老过程中的重复序列的高阶染色质结构的变化有助于衰老表型.
- hSATII分解和相关的炎症基因表达可能直接促进癌症的进展.
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