TRIM24 links a non-canonical histone signature to breast cancer Journal Article

   

Authors:	Tsai, W. W.; Wang, Z.; Yiu, T. T.; Akdemir, K. C.; Xia, W.; Winter, S.; Tsai, C. Y.; Shi, X.; Schwarzer, D.; Plunkett, W.; Aronow, B.; Gozani, O.; Fischle, W.; Hung, M. C.; Patel, D. J.; Barton, M. C.
Article Title:	TRIM24 links a non-canonical histone signature to breast cancer
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. © 2010 Macmillan Publishers Limited. All rights reserved.
Keywords:	cancer survival; controlled study; protein array analysis; survival rate; unclassified drug; major clinical study; methylation; cancer patient; protein domain; protein function; cell proliferation; gene overexpression; breast cancer; gene expression; protein; protein binding; estrogen; estrogens; cell line, tumor; breast neoplasms; gene expression regulation, neoplastic; histone; chromatin; three dimensional imaging; histone h3; carrier proteins; substrate specificity; crystallography, x-ray; protein structure, tertiary; pathogenicity; homeodomain protein; negative feedback; estrogen receptor; protein structure; breast carcinogenesis; histones; lysine; womens health; chromatin assembly and disassembly; acetylation; hek293 cells; peptides and proteins; tripartite motif containing 24 protein; estrogen receptor alpha
Journal Title:	Nature
Volume:	468
Issue:	7326
ISSN:	0028-0836
Publisher:	Nature Publishing Group
Date Published:	2010-12-16
Start Page:	927
End Page:	932
Language:	English
DOI:	10.1038/nature09542
PUBMED:	21164480
PROVIDER:	scopus
PMCID:	PMC3058826
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-78650353481&partnerID=40&md5=0f127f27919e121ec5461a1c84081067
Notes:	--- - "Export Date: 20 April 2011" - "CODEN: NATUA" - "Source: Scopus"

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