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TRPS1 regulates oestrogen receptor binding and histone acetylation at enhancers.

Accepted version
Peer-reviewed

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Article

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Authors

Serandour, AA 
Mohammed, H 
Miremadi, A 
Mulder, KW 
Carroll, JS 

Abstract

The chromatin state is finely tuned to regulate function and specificity for transcription factors such as oestrogen receptor alpha (ER), which contributes to cell growth in breast cancer. ER transcriptional potential is mediated, in large part, by the specific associated proteins and co-factors that interact with it. Despite the identification and characterisation of several ER coregulators, a complete and systematic view of ER-regulating chromatin modifiers is lacking. By exploiting a focused siRNA screen that investigated the requirement for a library of 330 chromatin regulators in ER-mediated cell growth, we find that the NuRD and coREST histone deacetylation complexes are critical for breast cancer cell proliferation. Further, by proteomic and genomics approaches, we discover the transcription factor TRPS1 to be a key interactor of the NuRD and coREST complexes. Interestingly, TRPS1 gene amplification occurs in 28% of human breast tumours and is associated with poor prognosis. We propose that TRPS1 is required to repress spurious binding of ER, where it contributes to the removal of histone acetylation. Our data suggest that TRPS1 is an important ER-associated transcriptional repressor that regulates cell proliferation, chromatin acetylation and ER binding at the chromatin of cis-regulatory elements.

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Keywords

Acetylation, Breast Neoplasms, Cell Line, Tumor, Co-Repressor Proteins, DNA-Binding Proteins, Female, Gene Expression Regulation, Neoplastic, Histones, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Nerve Tissue Proteins, Receptors, Estrogen, Repressor Proteins, Transcription Factors, Transcriptional Activation

Journal Title

Oncogene

Conference Name

Journal ISSN

0950-9232
1476-5594

Volume Title

Publisher

Nature
Sponsorship
Cancer Research UK (C14303/A17197)
European Research Council (242664)
European Research Council (646876)
Cancer Research UK (20411)