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Cited by 5Genomics and Chromatin DynamicsProtein Structure and DynamicsRNA Research and Splicing

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CBP-IDRs regulate acetylation and gene expression

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Gelder, Katie L., Carruthers, Nicola A., Gilbert, Grace, Harrison, Laura J., Evans, Brychan V., Evans, Thomas I., Ball, Sophie S., Dunning, Mark, Craggs, Timothy D., Twelvetrees, Alison E., Bose, Daniel A.·2026·Cell Reports
DOI 10.1016/j.celrep.2026.117109PMC PMC13013760

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Abstract

Intrinsically disordered regions (IDRs) are essential regulators of protein function despite lacking stable secondary and tertiary structures. IDRs are integral to the function of multidomain regulatory proteins, such as the essential transcriptional coactivators cAMP response element-binding protein (CREB)-binding protein (CBP) and EP300 (p300), but how their multiple IDRs work together to regulate function remains poorly understood. Here, we demonstrate that different CBP-IDRs cooperate to control complex nuclear behaviors. We show how CBP-IDRs with different sequence properties make unique contributions to CBP behavior, establishing a critical balance between positive and negative regulation of CBP condensates. These opposing interactions are functionally important, tuning CBP's sensitivity to regulatory cues such as lysine acetylation. Disruption of this balance fundamentally alters CBP's chromatin occupancy, patterns of histone acetylation, and downstream gene expression. Together, our work reveals an unexpected mechanism of intramolecular cooperation between distinct IDRs and highlights how their properties shape the functional landscape of multi-domain proteins.

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Metadata

Authors
Gelder, K. L., Carruthers, N. A., Gilbert, G., Harrison, L. J., Evans, B. V., Evans, T. I., Ball, S. S., Dunning, M., Craggs, T. D., Twelvetrees, A. E., & Bose, D. A.
Affiliations
University of Sheffield (GB)
Corresponding author
Bose, Daniel A.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2026-03
Volume
45
Issue
3
Pages
117109
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2026.117109
PMC
PMC13013760
OpenAlex
W7135046135
Cited by
5
References
4
Citations by year
2026: 2
FWCI
4.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
Funders
  • The Royal Society
  • Biotechnology and Biological Sciences Research Council
  • Wellcome Trust
  • UK Research and Innovation Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
intrinsically disordered regions, CREB-binding protein, EP300, lysine acetylation, protein condensates, histone acetylation, chromatin occupancy, gene expression regulation, transcriptional coactivator, multidomain proteins
MeSH terms
Acetylation, Animals, Chromatin, Gene Expression Regulation, Histones, Humans, Protein Binding, E1A-Associated p300 Protein, CREB-Binding Protein, HEK293 Cells, Intrinsically Disordered Proteins

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