Cohesin SMC1β promotes closed chromatin and controls TERRA expression at spermatocyte telomeres

Author:

Biswas Uddipta1,Deb Mallik Tanaya1ORCID,Pschirer Johannes1,Lesche Matthias2ORCID,Sameith Katrin2ORCID,Jessberger Rolf1ORCID

Affiliation:

1. Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden

2. Center for Molecular and Cellular Bioengineering, Genome Center Technology Platform, Dresden, Germany

Abstract

Previous data showed that meiotic cohesin SMC1β protects spermatocyte telomeres from damage. The underlying reason, however, remained unknown as the expressions of telomerase and shelterin components were normal inSmc1β−/−spermatocytes. Here. we report that SMC1β restricts expression of the long noncoding RNA TERRA (telomeric repeat containing RNA) in spermatocytes. In somatic cell lines increased TERRA was reported to cause telomere damage through altering telomere chromatin structure. InSmc1β−/−spermatocytes, we observed strongly increased levels of TERRA which accumulate on damaged chromosomal ends, where enhanced R-loop formation was found. This suggested a more open chromatin configuration near telomeres inSmc1β−/−spermatocytes, which was confirmed by ATAC-seq. Telomere-distal regions were not affected by the absence of SMC1β but RNA-seq revealed increased transcriptional activity in telomere-proximal regions. Thus, SMC1β promotes closed chromatin specifically near telomeres and limits TERRA expression in spermatocytes.

Funder

EU Horizon 2020

Deutsche Forschungsgemeinschaft

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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