Cited by 7Genomics and Chromatin DynamicsChromatin Remodeling and CancerProtein Structure and Dynamics

Intrinsically Disordered Regions Define Unique Protein Interaction Networks in CHD Family Remodelers

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Tabar, Mehdi Sharifi, Parsania, Chirag, Giardina, Caroline, Feng, Yue, Wong, Alex C. H., Metierre, Cynthia, Nagarajah, Rajini, Dhungel, Bijay P. +2 more·2025·The FASEB Journal

Published version of a preprint

Abstract

Chromodomain helicase DNA‐binding (CHD) enzymes play a pivotal role in genome regulation. They possess highly conserved ATPase domains flanked by poorly characterized and intrinsically disordered N‐ and C‐termini. Using mass spectrometry, we identify dozens of novel protein–protein interactions (PPIs) within the N‐ and C‐termini of human CHD family members. We also define a highly conserved aggregation‐prone region (APR) within the C‐terminus of CHD4 which is critical for its interaction with the nucleosome remodeling and deacetylase (NuRD), as well as ChAHP (CHD4, activity‐dependent neuroprotective protein (ADNP), and HP1γ) complexes. Further analysis reveals a regulatory role for the CHD4 APR in gene transcription during erythrocyte formation. Our results highlight that the N‐ and C‐termini of CHD chromatin remodelers shape protein interaction networks that drive unique transcriptional programs.

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Authors
Tabar, M. S., Parsania, C., Giardina, C., Feng, Y., Wong, A. C. H., Metierre, C., Nagarajah, R., Dhungel, B. P., Rasko, J. E. J., & Bailey, C. G.
Affiliations
  • The University of Sydney (AU)
  • Royal Prince Alfred Hospital (AU)
Corresponding author
  • Rasko, John E. J.
  • Bailey, Charles G.
Venue
The FASEB Journal
Publisher
Wiley
Published
2025-05-15
Volume
39
Issue
10
Pages
e70632-e70632
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
OpenAlex
W4410400478
Cited by
7
References
5
Citations by year
2026: 6 · 2025: 1
FWCI
2.10
Type
journal article
Language
en
Open access
Locations
  • The FASEB Journal (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Health and Medical Research Council (#1177305, #1128748)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
CHD4, intrinsically disordered regions, protein-protein interaction, protein termini, aggregation-prone regions, NuRD complex, ADNP, HP1γ, chromatin remodeling, gene transcription, erythroid differentiation, genome regulation
MeSH terms
DNA Helicases, DNA-Binding Proteins, Humans, Chromatin Assembly and Disassembly, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Protein Interaction Maps, Intrinsically Disordered Proteins

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