H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction

Sean E. Healton, Hugo D. Pinto, Laxmi N. Mishra, Gregory A. Hamilton, Gregory A. Hamilton, Justin C. Wheat, Kalina Swist-Rosowska, Nicholas Shukeir, Yali Dou, Ulrich Steidl, Thomas Jenuwein, Matthew J. Gamble, Matthew J. Gamble, Arthur I. Skoultchi

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Nearly 50% of mouse and human genomes are composed of repetitive sequences. Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker histones in silencing repetitive elements in mouse embryonic stem cells. Strong H1 depletion causes a profound de-repression of several classes of repetitive sequences, including major satellite, LINE-1, and ERV. Activation of repetitive sequence transcription is accompanied by decreased H3K9 trimethylation of repetitive sequence chromatin. H1 linker histones interact directly with Suv39h1, Suv39h2, and SETDB1, the histone methyltransferases responsible for H3K9 trimethylation of chromatin within these regions, and stimulate their activity toward chromatin in vitro. However, we also implicate chromatin compaction mediated by H1 as an additional, dominant repressive mechanism for silencing of repetitive major satellite sequences. Our findings elucidate two distinct, H1-mediated pathways for silencing heterochromatin.

Original languageEnglish (US)
Pages (from-to)14251-14258
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number25
DOIs
StatePublished - Jun 23 2020

Keywords

  • Chromatin
  • Epigenetics
  • Linker histones
  • Repetitive elements

ASJC Scopus subject areas

  • General

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    Healton, S. E., Pinto, H. D., Mishra, L. N., Hamilton, G. A., Hamilton, G. A., Wheat, J. C., Swist-Rosowska, K., Shukeir, N., Dou, Y., Steidl, U., Jenuwein, T., Gamble, M. J., Gamble, M. J., & Skoultchi, A. I. (2020). H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction. Proceedings of the National Academy of Sciences of the United States of America, 117(25), 14251-14258. https://doi.org/10.1073/pnas.1920725117