CHD1 Loss Alters AR Binding at Lineage-Specific Enhancers and Modulates Distinct Transcriptional Programs to Drive Prostate Tumorigenesis.
Publisher DOI
PubMed ID
30930119
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.
Date Issued
2019-04-15
Publication Type
Article
Subject(s)
Subjects
AR CHD1 HOXB13 androgen receptor chromatin remodeling cistrome reprogramming epigenetics interactome prostate cancer prostate cancer subclass
Language(s)
en
Author(s)
Augello, Michael A | |
Liu, Deli | |
Deonarine, Lesa D | |
Robinson, Brian D | |
Huang, Dennis | |
Stelloo, Suzan | |
Blattner, Mirjam | |
Doane, Ashley S | |
Wong, Elissa W P | |
Chen, Yu | |
Beltran, Himisha | |
Elemento, Olivier | |
Bergman, Andries M | |
Zwart, Wilbert | |
Sboner, Andrea | |
Dephoure, Noah | |
Barbieri, Christopher E |
Journal
Cancer cell
Publisher
Cell Press
ISSN
1535-6108
Access(Rights)
restricted