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PreprintCited 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.·2024·Cell Reports
DOI 10.1101/2024.06.04.597392PMC PMC13013760

Preprint — published as 10.1016/j.celrep.2026.117109 · Paper page

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Abstract

Intrinsically disordered regions (IDRs) have emerged as crucial regulators of protein function, allowing proteins to sense and respond to their environment. Creb binding protein (CBP) and EP300 (p300) are transcription coactivators that regulate gene expression in multicellular organisms, following their recruitment to cis -regulatory elements. CBP and p300 contain large IDRs, however little is known about how these different IDRs work together to regulate CBP function. Here, we show that CBP-IDRs cooperate to control different aspects of CBP behaviour in the nucleus, by regulating the properties of fluid-like condensates formed by endogenous CBP. We show how IDRs with different sequence properties make unique contributions to CBP behaviour by establishing a balance between positive and negative regulation of CBP condensates. These conflicting interactions are functionally important, shaping CBPs response to factors such as lysine acetylation, that influence condensate formation. When disrupted, regulatory CBP-IDRs change how CBP interacts with chromatin, alter patterns of CBP-dependent histone acetylation and change gene expression. Together, our work highlights how IDRs with different sequences, spatially segregated in the same protein, can cooperate to shape protein function.

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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
openRxiv
Published
2024-06-04
Volume
45
Issue
3
Pages
117109-117109
ISSN
2211-1247 (ISSN-L)
DOI
10.1101/2024.06.04.597392
PMC
PMC13013760
OpenAlex
W7135046135
Cited by
5
References
1
Citations by year
2026: 2 · 2024: 3
FWCI
4.06
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
  • Wellcome Trust (213501/Z/18/Z, 220192/Z/20/Z)
  • Biotechnology and Biological Sciences Research Council (BB/Y513453/1, BB/M011151/1, BB/T008032/1)
  • Medical Research Council (MR/N013840)
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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