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PreprintCited by 11Genomics and Chromatin DynamicsNuclear Structure and FunctionEpigenetics and DNA Methylation

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Structural mechanism of HP1α-dependent transcriptional repression and chromatin compaction

Open access
Sokolova, Vladyslava, Miratsky, Jacob, Svetlov, Vladimir, Brenowitz, Michael, Vant, John, Lewis, Tyler, Dryden, Kelly, Lee, Gahyun, Sarkar, Shayan, Nudler, Evgeny, Singharoy, Abhishek, Tan, Dongyan·2023·Structure
DOI 10.1101/2023.11.30.569387PMC PMC11560701

Preprint — published as 10.1016/j.str.2024.09.013 · Paper page

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Abstract

Heterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions and their contributions to heterochromatin functions remain elusive. In this study, we employed a multidisciplinary approach to unravel the interactions between human HP1α and nucleosomes. We have elucidated the cryo-EM structure of an HP1α dimer bound to an H2A.Z nucleosome, revealing that the HP1α dimer interfaces with nucleosomes at two distinct sites. The primary binding site is located at the N-terminus of histone H3, specifically at the trimethylated K9 (K9me3) region, while a novel secondary binding site is situated near histone H2B, close to nucleosome superhelical location 4 (SHL4). Our biochemical data further demonstrates that HP1α binding influences the dynamics of DNA on the nucleosome. It promotes DNA unwrapping near the nucleosome entry and exit sites while concurrently restricting DNA accessibility in the vicinity of SHL4. This study offers a model that explains how HP1α functions in heterochromatin maintenance and gene silencing, particularly in the context of H3K9me-dependent mechanisms. Additionally, it sheds light on the H3K9me-independent role of HP1 in responding to DNA damage.

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Metadata

Authors
Sokolova, V., Miratsky, J., Svetlov, V., Brenowitz, M., Vant, J., Lewis, T., Dryden, K., Lee, G., Sarkar, S., Nudler, E., Singharoy, A., & Tan, D.
Affiliations
  • Stony Brook University (US)
  • Arizona State University (US)
  • Howard Hughes Medical Institute (US)
  • Albert Einstein College of Medicine (US)
  • University of Virginia (US)
Corresponding author
Tan, Dongyan
ORCID
Venue
Structure
Publisher
openRxiv
Published
2023-11-30
Volume
32
Issue
11
Pages
2094-2106.e6
ISSN
0969-2126 (ISSN-L)
DOI
10.1101/2023.11.30.569387
PMC
PMC11560701
OpenAlex
W4403223236
Cited by
11
References
1
Citations by year
2026: 7 · 2025: 4
FWCI
1.50
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Structure (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • National Science Foundation (1942049, 1S10OD012272-01A1, SCR_019031)
  • U.S. Department of Energy (KP1607011)
  • National Institutes of Health (5r35gm133611-02, SCR_019031, 1s10od012272-01a1, 1R35GM133611)
  • School of Medicine (G20-RR31199, S10-RR025067, U24-GM116790)
  • National Institute of General Medical Sciences (R35GM133611, U24GM116790)
  • National Center for Research Resources (S10RR025067, G20RR031199)
  • Biological and Environmental Research (KP1607011)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
HP1α, HP1, transcriptional repression, chromatin condensation, heterochromatin maintenance, DNA accessibility, gene silencing, DNA damage response

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