Multimodal interactions drive chromatin phase separation and compaction

Tina Ukmar-Godec, Maria Sol Cima-Omori, Zhadyra Yerkesh, Karthik Eswara, Taekyung Yu, Reshma Ramesh, Gwladys Riviere, Alain Ibanez de Opakua, Wolfgang Fischle, Markus Zweckstetter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Gene silencing is intimately connected to DNA condensation and the formation of transcriptionally inactive heterochromatin by Heterochromatin Protein 1α (HP1α). Because heterochromatin foci are dynamic and HP1α can promote liquid–liquid phase separation, HP1α-mediated phase separation has been proposed as a mechanism of chromatin compaction. The molecular basis of HP1α-driven phase separation and chromatin compaction and the associated regulation by trimethylation of lysine 9 in histone 3 (H3K9me3), which is the hallmark of constitutive heterochromatin, is however largely unknown. Using a combination of chromatin compaction and phase separation assays, site-directed mutagenesis, and NMR-based interaction analysis, we show that human HP1α can compact chromatin in the absence of liquid–liquid phase separation. We further demonstrate that H3K9-trimethylation promotes compaction of chromatin arrays through multimodal interactions. The results provide molecular insights into HP1α-mediated chromatin compaction and thus into the role of human HP1α in the regulation of gene silencing.

Original languageEnglish (US)
Article numbere2308858120
JournalPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume120
Issue number50
DOIs
StatePublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 National Academy of Sciences. All rights reserved.

ASJC Scopus subject areas

  • General

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