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Publication

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

Cancer cell | 2019

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.

Pubmed ID: 30930119 RIS Download

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Associated grants

Agency: NCI NIH HHS, United States
Id: R01 CA233650
Agency: NCI NIH HHS, United States
Id: P30 CA008748
Agency: NCI NIH HHS, United States
Id: R37 CA215040
Agency: NCI NIH HHS, United States
Id: K08 CA187417
Agency: NCI NIH HHS, United States
Id: P50 CA211024

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