Cross-talk between chromatin acetylation and SUMOylation of tripartite motif–containing protein 24 (TRIM24) impacts cell adhesion

Srikanth Appikonda, Kaushik N. Thakkar, Parantu K. Shah, Sharon Y.R. Dent, Jannik N. Andersen, Michelle C. Barton

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Proteins with domains that recognize and bind post-translational modifications (PTMs) of histones are collectively termed epigenetic readers. Numerous interactions between specific reader protein domains and histone PTMs and their regulatory outcomes have been reported, but little is known about how reader proteins may in turn be modulated by these interactions. Tripartite motif– containing protein 24 (TRIM24) is a histone reader aberrantly expressed in multiple cancers. Here, our investigation revealed functional cross-talk between histone acetylation and TRIM24 SUMOylation. Binding of TRIM24 to chromatin via its tandem PHD-bromodomain, which recognizes unmethylated lysine 4 and acetylated lysine 23 of histone H3 (H3K4me0/K23ac), led to TRIM24 SUMOylation at lysine residues 723 and 741. Inactivation of the bromodomain, either by mutation or with a small-molecule inhibitor, IACS-9571, abolished TRIM24 SUMOylation. Conversely, inhibition of histone deacetylation markedly increased TRIM24’s interaction with chromatin and its SUMOylation. Of note, gene expression profiling of MCF7 cells expressing WT versus SUMO-deficient TRIM24 identified cell adhesion as the major pathway regulated by the cross-talk between chromatin acetylation and TRIM24 SUMOylation. In conclusion, our findings establish a new link between histone H3 acetylation and SUMOylation of the reader protein TRIM24, a functional connection that may bear on TRIM24’s oncogenic function and may inform future studies of PTM cross-talk between histones and epigenetic regulators.

Original languageEnglish (US)
Pages (from-to)7476-7485
Number of pages10
JournalJournal of Biological Chemistry
Volume293
Issue number19
DOIs
StatePublished - May 11 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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