Pericentromeric repetitive ncRNA regulates chromatin interaction and inflammatory gene expression

Kenichi Miyata; Akiko Takahashi

doi:10.1080/19491034.2022.2034269

Pericentromeric repetitive ncRNA regulates chromatin interaction and inflammatory gene expression

Nucleus. 2022 Dec;13(1):74-78. doi: 10.1080/19491034.2022.2034269.

Authors

Kenichi Miyata^{1

2}, Akiko Takahashi^{1

2

3}

Affiliations

¹ Project for Cellular Senescence, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
² Cancer Cell Communication Project, NEXT-Ganken Program, Japanese Foundation for Cancer Research, Tokyo, Japan.
³ Advanced Research & Development Programs for Medical Innovation (PRIME), Japan Agency for Medical Research and Development (Amed), Tokyo, Japan.

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.

Keywords: CTCF; Cellular senescence; pericentromeric RNA; senescence-associated secretory phenotype; small extracellular vesicles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CCCTC-Binding Factor / metabolism
Cellular Senescence / genetics
Chromatin* / genetics
Gene Expression
Gene Expression Regulation
RNA, Untranslated* / genetics
Senescence-Associated Secretory Phenotype

Substances

CCCTC-Binding Factor
Chromatin
RNA, Untranslated

Grants and funding

This work was supported, in part, by grants from the Japan Agency of Medical Research and Development (No. 19gm6110023h0001), from the Japan Science and Technology Agency-Moonshot R&D (No. JPMJPS2022) and from the Japan Society for the Promotion of Science (No. 20K16344). This research was also supported by the Research Fellowships for Young Scientists from JSPS (No. 19J00796).