着丝粒周围重复 ncRNA 调节染色质相互作用和炎症基因表达。
Pericentromeric repetitive ncRNA regulates chromatin interaction and inflammatory gene expression.
机构信息
Project for Cellular Senescence, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
Cancer Cell Communication Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, Japan.
出版信息
Nucleus. 2022 Dec;13(1):74-78. doi: 10.1080/19491034.2022.2034269.
Cellular senescence provokes a dramatic alteration of chromatin organization and gene expression profile of proinflammatory factors, thereby contributing to various age-related pathologies via the senescence-associated secretory phenotype (SASP). Chromatin organization and global gene expression are maintained through the CCCTC-binding factor (CTCF). However, the molecular mechanism underlying CTCF regulation and its association with SASP gene expression remains to be fully elucidated. A recent study by our team showed that noncoding RNA (ncRNA) derived from normally silenced pericentromeric repetitive sequences directly impair the DNA binding of CTCF. This CTCF disturbance increases the accessibility of chromatin at the loci of SASP genes and caused the transcription of inflammatory factors. This mechanism may promote malignant transformation.
细胞衰老会引起染色质组织和促炎因子基因表达谱的显著改变，从而通过衰老相关分泌表型（SASP）导致各种与年龄相关的病理。染色质组织和全局基因表达是通过 CCCTC 结合因子（CTCF）维持的。然而，CTCF 调节的分子机制及其与 SASP 基因表达的关联仍有待充分阐明。我们团队的一项最新研究表明，来自正常沉默的着丝粒重复序列的非编码 RNA（ncRNA）直接损害 CTCF 的 DNA 结合。这种 CTCF 干扰增加了 SASP 基因位点的染色质可及性，并导致炎症因子的转录。这种机制可能促进恶性转化。
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