BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1

English version

Autoři: Shu Wu ^aff001; Yuanlong Ge ^aff002; Xiaocui Li ^aff001; Yiding Yang ^aff001; Haoxian Zhou ^aff001; Kaixuan Lin ^aff003; Zepeng Zhang ^aff002; Yong Zhao ^aff001
Působiště autorů: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China ^aff001; Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China ^aff002; Yale Stem Cell Center & Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America ^aff003
Vyšlo v časopise: BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008799
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008799

Souhrn

TRF2 and TRF1 are a key component in shelterin complex that associates with telomeric DNA and protects chromosome ends. BRM is a core ATPase subunit of SWI/SNF chromatin remodeling complex. Whether and how BRM-SWI/SNF complex is engaged in chromatin end protection by telomeres is unknown. Here, we report that depletion of BRM does not affect heterochromatin state of telomeres, but results in telomere dysfunctional phenomena including telomere uncapping and replication defect. Mechanistically, expression of TRF2 and TRF1 is jointly regulated by BRM-SWI/SNF complex, which is localized to promoter region of both genes and facilitates their transcription. BRM-deficient cells bear increased TRF2-free or TRF1-free telomeres due to insufficient expression. Importantly, BRM depletion-induced telomere uncapping or replication defect can be rescued by compensatory expression of exogenous TRF2 or TRF1, respectively. Together, these results identify a new function of BRM-SWI/SNF complex in enabling functional telomeres for maintaining genome stability.

Klíčová slova:

Apoptosis – Gene expression – Genome complexity – HeLa cells – Chromatin – Micronuclei – Small interfering RNAs – Telomeres

Zdroje

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