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

Michael A. Augello, Deli Liu, Lesa D. Deonarine, Brian D. Robinson, Dennis Huang, Suzan Stelloo, Mirjam Blattner, Ashley S. Doane, Elissa W.P. Wong, Yu Chen, Mark A. Rubin, Himisha Beltran, Olivier Elemento, Andries M. Bergman, Wilbert Zwart, Andrea Sboner, Noah Dephoure, Christopher E. Barbieri (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

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.

LanguageEnglish
Pages603-617
JournalCancer Cell
Volume35
Issue number4
DOIs
StatePublished - 15 Apr 2019

Fingerprint

Androgen Receptors
Prostate
Carcinogenesis
Neoplasms
Prostatic Neoplasms
Gene Deletion
Chromatin

Keywords

  • androgen receptor
  • AR
  • CHD1
  • chromatin remodeling
  • cistrome reprogramming
  • epigenetics
  • HOXB13
  • interactome
  • prostate cancer
  • prostate cancer subclass

Cite this

Augello, M. A., Liu, D., Deonarine, L. D., Robinson, B. D., Huang, D., Stelloo, S., ... Barbieri, C. E. (2019). CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis. Cancer Cell, 35(4), 603-617. DOI: 10.1016/j.ccell.2019.03.001
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./ CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis. In: Cancer Cell. 2019 ; Vol. 35, No. 4. pp. 603-617
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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.",
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Augello, 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 2019, 'CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis' Cancer Cell, vol. 35, no. 4, pp. 603-617. DOI: 10.1016/j.ccell.2019.03.001

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.

Research output: Contribution to journalArticleAcademicpeer-review

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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.

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KW - prostate cancer subclass

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DO - 10.1016/j.ccell.2019.03.001

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T2 - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

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Augello MA, Liu D, Deonarine LD, Robinson BD, Huang D, Stelloo S et al. CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis. Cancer Cell. 2019 Apr 15;35(4):603-617. Available from, DOI: 10.1016/j.ccell.2019.03.001