Gale and Ira Drukier Institute for Children's Health

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CHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis.

TitleCHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis.
Publication TypeJournal Article
Year of Publication2019
AuthorsAugello MA, Liu D, Deonarine LD, Robinson BD, Huang D, Stelloo S, Blattner M, Doane AS, Wong EWP, Chen Y, Rubin MA, Beltran H, Elemento O, Bergman AM, Zwart W, Sboner A, Dephoure N, Barbieri CE
JournalCancer Cell
Volume35
Issue4
Pagination603-617.e8
Date Published2019 Apr 15
ISSN1878-3686
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.

DOI10.1016/j.ccell.2019.03.001
Alternate JournalCancer Cell
PubMed ID30930119
PubMed Central IDPMC6467783
Grant ListK08 CA187417 / CA / NCI NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States
R37 CA215040 / CA / NCI NIH HHS / United States