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TRIM24 links a non-canonical histone signature to breast cancer.

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.

Pubmed ID: 21164480


  • Tsai WW
  • Wang Z
  • Yiu TT
  • Akdemir KC
  • Xia W
  • Winter S
  • Tsai CY
  • Shi X
  • Schwarzer D
  • Plunkett W
  • Aronow B
  • Gozani O
  • Fischle W
  • Hung MC
  • Patel DJ
  • Barton MC



Publication Data

December 16, 2010

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM079641
  • Agency: NIGMS NIH HHS, Id: GM081627
  • Agency: NIGMS NIH HHS, Id: P01 GM081627
  • Agency: NIGMS NIH HHS, Id: P01 GM081627-010003
  • Agency: NIGMS NIH HHS, Id: P01 GM081627-020003
  • Agency: NIBIB NIH HHS, Id: P30 EB009998
  • Agency: NIDDK NIH HHS, Id: P30DK078392-01
  • Agency: NICHD NIH HHS, Id: T32 HD07325
  • Agency: NCRR NIH HHS, Id: U54 RR025216
  • Agency: NCATS NIH HHS, Id: UL1 TR000077

Mesh Terms

  • Acetylation
  • Breast Neoplasms
  • Carrier Proteins
  • Cell Line, Tumor
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Crystallography, X-Ray
  • Estrogen Receptor alpha
  • Estrogens
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Histones
  • Humans
  • Methylation
  • Protein Array Analysis
  • Protein Binding
  • Protein Structure, Tertiary
  • Substrate Specificity
  • Survival Rate