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.
| Original language | English |
|---|---|
| Pages (from-to) | 603-617.e8 |
| Journal | Cancer Cell |
| Volume | 35 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 15 Apr 2019 |
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Keywords
- androgen receptor
- AR
- CHD1
- chromatin remodeling
- cistrome reprogramming
- epigenetics
- HOXB13
- interactome
- prostate cancer
- prostate cancer subclass
Cite this
}
CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis. / 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; Rubin, Mark A.; Beltran, Himisha; Elemento, Olivier; Bergman, Andries M.; Zwart, Wilbert; Sboner, Andrea; Dephoure, Noah; Barbieri, Christopher E. (Corresponding author).
In: Cancer Cell, Vol. 35, No. 4, 15.04.2019, p. 603-617.e8.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis
AU - Augello, Michael A.
AU - Liu, Deli
AU - Deonarine, Lesa D.
AU - Robinson, Brian D.
AU - Huang, Dennis
AU - Stelloo, Suzan
AU - Blattner, Mirjam
AU - Doane, Ashley S.
AU - Wong, Elissa W.P.
AU - Chen, Yu
AU - Rubin, Mark A.
AU - Beltran, Himisha
AU - Elemento, Olivier
AU - Bergman, Andries M.
AU - Zwart, Wilbert
AU - Sboner, Andrea
AU - Dephoure, Noah
AU - Barbieri, Christopher E.
PY - 2019/4/15
Y1 - 2019/4/15
N2 - 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.
AB - 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.
KW - androgen receptor
KW - AR
KW - CHD1
KW - chromatin remodeling
KW - cistrome reprogramming
KW - epigenetics
KW - HOXB13
KW - interactome
KW - prostate cancer
KW - prostate cancer subclass
UR - http://www.scopus.com/inward/record.url?scp=85064090666&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2019.03.001
DO - 10.1016/j.ccell.2019.03.001
M3 - Article
C2 - 30930119
AN - SCOPUS:85064090666
VL - 35
SP - 603-617.e8
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 4
ER -