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)

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Uittreksel

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.

TaalEngels
Pagina's603-617
TijdschriftCancer Cell
Volume35
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 15 apr 2019

Vingerafdruk

Androgen Receptors
Prostate
Carcinogenesis
Neoplasms
Prostatic Neoplasms
Gene Deletion
Chromatin

Trefwoorden

    Citeer dit

    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, Nr. 4. blz. 603-617
    @article{15f572d84ae94fc0876b1e5a74629433,
    title = "CHD1 loss alters AR binding at lineage-specific enhancers and modulates distinct transcriptional programs to drive prostate tumorigenesis",
    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.",
    keywords = "androgen receptor, AR, CHD1, chromatin remodeling, cistrome reprogramming, epigenetics, HOXB13, interactome, prostate cancer, prostate cancer subclass",
    author = "Augello, {Michael A.} and Deli Liu and Deonarine, {Lesa D.} and Robinson, {Brian D.} and Dennis Huang and Suzan Stelloo and Mirjam Blattner and Doane, {Ashley S.} and Wong, {Elissa W.P.} and Yu Chen and Rubin, {Mark A.} and Himisha Beltran and Olivier Elemento and Bergman, {Andries M.} and Wilbert Zwart and Andrea Sboner and Noah Dephoure and Barbieri, {Christopher E.}",
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    language = "English",
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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, nr. 4, blz. 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, Nr. 4, 15.04.2019, blz. 603-617.

    Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer 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

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    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.

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    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.

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    KW - chromatin remodeling

    KW - cistrome reprogramming

    KW - epigenetics

    KW - HOXB13

    KW - interactome

    KW - prostate cancer

    KW - prostate cancer subclass

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    U2 - 10.1016/j.ccell.2019.03.001

    DO - 10.1016/j.ccell.2019.03.001

    M3 - Article

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    SP - 603

    EP - 617

    JO - Cancer Cell

    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. Beschikbaar vanaf, DOI: 10.1016/j.ccell.2019.03.001