TRIM24 links a non-canonical histone signature to breast cancer

Wen Wei Tsai, Zhanxin Wang, Teresa T. Yiu, Kadir C. Akdemir, Weiya Xia, Stefan Winter, Cheng Yu Tsai, Xiaobing Shi, Dirk Schwarzer, William Plunkett, Bruce Aronow, Or Gozani, Wolfgang Fischle, Mien Chie Hung, Dinshaw J. Patel, Michelle Craig Barton

Research output: Contribution to journalArticlepeer-review

274 Scopus citations

Abstract

Recognition of modified histone species by distinct structural domains within reader proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.

Original languageEnglish (US)
Pages (from-to)927-932
Number of pages6
JournalNature
Volume468
Issue number7326
DOIs
StatePublished - Dec 16 2010
Externally publishedYes

ASJC Scopus subject areas

  • General

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