CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis Journal Article

   


Authors: Augello, M. A.; Liu, D.; Deonarine, L. D.; Robinson, B. D.; Huang, D.; Stelloo, S.; Blattner, M.; Doane, A. S.; Wong, E. W. P.; Chen, Y.; Rubin, M. A.; Beltran, H.; Elemento, O.; Bergman, A. M.; Zwart, W.; Sboner, A.; Dephoure, N.; Barbieri, C. E.
Article Title: CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis
Abstract: Deletion of the gene encoding the chromatin remodeler CHD1 is among the most common alterations in prostate cancer (PCa); however, the tumor-suppressive functions of CHD1 and reasons for its tissue-specific loss remain undefined. We demonstrated that CHD1 occupied prostate-specific enhancers enriched for the androgen receptor (AR) and lineage-specific cofactors. Upon CHD1 loss, the AR cistrome was redistributed in patterns consistent with the oncogenic AR cistrome in PCa samples and drove tumor formation in the murine prostate. Notably, this cistrome shift was associated with a unique AR transcriptional signature enriched for pro-oncogenic pathways unique to this tumor subclass. Collectively, these data credential CHD1 as a tumor suppressor in the prostate that constrains AR binding/function to limit tumor progression. © 2019 Elsevier Inc. Augello et al. show that CHD1 binds prostate-specific enhancers enriched for the androgen receptor (AR). Upon CHD1 loss, which occurs often in prostate cancer (PCa), the AR cistrome changes to be consistent with that in PCa and is associated with an AR transcriptional signature unique to this subclass of PCa. © 2019 Elsevier Inc.
Keywords: prostate cancer; epigenetics; androgen receptor; ar; interactome; chromatin remodeling; chd1; cistrome reprogramming; hoxb13; prostate cancer subclass
Journal Title: Cancer Cell
Volume: 35
Issue: 4
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2019-04-15
Start Page: 603
End Page: 617.e8
Language: English
DOI: 10.1016/j.ccell.2019.03.001
PUBMED: 30930119
PROVIDER: scopus
PMCID: PMC6467783
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064090666&doi=10.1016%2fj.ccell.2019.03.001&partnerID=40&md5=67d4f876208aa983b1af86ffb60dfe16
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
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