Pericentromeric repetitive ncRNA regulates chromatin interaction and inflammatory gene expression.

Abstract

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.