Recruitment of the mammalian histone-modifying EMSY complex to target genes is regulated by ZNF131

Radhika A. Varier, Enrique Carrillo De Santa Pau, Petra Van Der Groep, Rik G.H. Lindeboom, Filomena Matarese, Anneloes Mensinga, Arne H. Smits, Raghu Ram Edupuganti, Marijke P. Baltissen, Pascal W.T.C. Jansen, Natalie Ter Hoeve, Danny R. Van Weely, Ina Poser, Paul J. Van Diest, Hendrik G. Stunnenberg, Michiel Vermeulen

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

Recent work from others and us revealed interactions between the Sin3/HDAC complex, the H3K4me3 demethylase KDM5A, GATAD1, and EMSY. Here, we characterize the EMSY/KDM5A/SIN3B complex in detail by quantitative interaction proteomics and ChIP-sequencing. We identify a novel substoichiometric interactor of the complex, transcription factor ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. Interestingly, using an EMSY knock-out line and subsequent rescue experiments, we show that EMSY is in most cases positively correlated with transcriptional activity of its target genes and stimulates cell proliferation. Finally, by immunohistochemical staining of primary breast tissue microarrays we find that EMSY/KDM5A/SIN3B complex subunits are frequently overexpressed in primary breast cancer cases in a correlative manner. Taken together, these data open venues for exploring the possibility that sporadic breast cancer patients with EMSY amplification might benefit from epigenetic combination therapy targeting both the KDM5A demethylase and histone deacetylases.

Original languageEnglish
Pages (from-to)7313-7324
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number14
DOIs
Publication statusPublished - 1 Apr 2016
Externally publishedYes

Fingerprint

Dive into the research topics of 'Recruitment of the mammalian histone-modifying EMSY complex to target genes is regulated by ZNF131'. Together they form a unique fingerprint.

Cite this