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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2016 (archival)     Display Documents

ID: 732416.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2016 (archival)
Recruitment of the Mammalian Histone-modifying EMSY Complex to Target Genes Is Regulated by ZNF131.
Authors:Varier, Radhika A; Pau, Enrique Carrillo de Santa; Groep, Petra van der; Lindeboom, Rik G H; Matarese, Filomena; Mensinga, Anneloes; Smits, Arne H; Edupuganti, Raghu Ram; Baltissen, Marijke P; Jansen, Pascal W T C; Hoeve, Natalie Ter; Weely, Danny R van; Poser, Ina; Diest, Paul J van; Stunnenberg, Hendrik G; Vermeulen, Michiel
Date of Publication (YYYY-MM-DD):2016
Title of Journal:The Journal of Biological Chemistry
Issue / Number:14
Start Page:7313
End Page:7324
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
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