SINHCAF/FAM60A and SIN3A specifically repress HIF 2α expression

Biddlestone, J., Batie, M., Bandarra, D., Munoz, I. and Rocha, S. (2018) SINHCAF/FAM60A and SIN3A specifically repress HIF 2α expression. Biochemical Journal, 475(12), pp. 2073-2090. (doi:10.1042/BCJ20170945) (PMID:29784889) (PMCID:PMC6024822)

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Abstract

The SIN3A–HDAC (histone deacetylase) complex is a master transcriptional repressor, required for development but often deregulated in disease. Here, we report that the recently identified new component of this complex, SINHCAF (SIN3A and HDAC-associated factor)/FAM60A (family of homology 60A), links the SIN3A–HDAC co-repressor complex function to the hypoxia response. We show that SINHCAF specifically represses HIF-2α mRNA and protein expression, via its interaction with the transcription factor SP1 (specificity protein 1) and recruitment of HDAC1 to the HIF-2α promoter. SINHCAF control over HIF-2α results in functional cellular changes in in vitro angiogenesis and viability. Our analysis reveals an unexpected link between SINHCAF and the regulation of the hypoxia response.

Item Type:Articles
Additional Information:J.B. was funded by a Cancer Research UK clinical fellowship. D.B. was funded by a PhD studentship from the Portuguese Science Foundation and Graduate Program in Areas of Basic and Applied Biology (GABBA). M.B. was funded by an MRC PhD studentship. S.R. was funded by a Cancer Research UK Senior Research Fellowship C99667/A12918. This work was also supported by a Wellcome Trust Strategic Award [097945/B/11/Z] and additionally supported by a small grant from the Anne and Normile Baxter prize for cancer research 2014.
Keywords:Hypoxia, SIN3A, SP1, histone deacetylases, hypoxia inducible factors, trancription.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Biddlestone, Dr John
Authors: Biddlestone, J., Batie, M., Bandarra, D., Munoz, I., and Rocha, S.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Biochemical Journal
Publisher:Portland Press
ISSN:0264-6021
ISSN (Online):1470-8728
Published Online:21 May 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Biochemical Journal 475(12):2073-2090
Publisher Policy:Reproduced under a Creative Commons License

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