Definition of a FoxA1 cistrome that is crucial for G 1 to S-phase cell-cycle transit in castration-resistant prostate cancer

Chunpeng Zhang, Liguo Wang, Dayong Wu, Hongyan Chen, Zhong Chen, Jennifer M. Thomas-Ahner, Debra L. Zynger, Jérôme Eeckhoute, Jindan Yu, Jun Luo, Myles Brown, Steven K. Clinton, Kenneth Nephew, Tim H M Huang, Wei Li, Qianben Wang

Research output: Contribution to journalArticle

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Abstract

The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid receptor (SR) action in hormone-dependent cancers. In castration-resistant prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G 2 to M-phase cell-cycle transit. Here, we describe a mechanistically distinct SRindependent role for FoxA1 in driving G 1 to S-phase cell-cycle transit in CRPC. By comparing FoxA1 binding sites in prostate cancer cell genomes, we defined a codependent set of FoxA1-MYBL2 and FoxA1-CREB1 binding sites within the regulatory regions of the Cyclin E2 and E2F1 genes that are critical for CRPC growth. Binding at these sites upregulate the Cyclin E2 and Cyclin A2 genes in CRPC but not in earlier stage androgen-dependent prostate cancer, establishing a stage-specific role for this pathway in CRPC growth. Mechanistic investigations indicated that FoxA1, MYBL2, or CREB1 induction of histone H3 acetylation facilitated nucleosome disruption as the basis for codependent transcriptional activation and G 1 to S-phase cell-cycle transit. Our findings establish FoxA1 as a pivotal driver of the cell-cycle in CRPC which promotes G 1 to S-phase transit as well as G 2 to M-phase transit through two distinct mechanisms.

Original languageEnglish
Pages (from-to)6738-6748
Number of pages11
JournalCancer Research
Volume71
Issue number21
DOIs
StatePublished - Nov 1 2011

Fingerprint

Castration
S Phase
Prostatic Neoplasms
Cell Cycle
Cyclins
Binding Sites
Cell Division
Cyclin A2
Nucleosomes
Steroid Receptors
Nucleic Acid Regulatory Sequences
Androgen Receptors
Acetylation
Growth
Histones
Transcriptional Activation
Androgens
Genes
Transcription Factors
Up-Regulation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Definition of a FoxA1 cistrome that is crucial for G 1 to S-phase cell-cycle transit in castration-resistant prostate cancer. / Zhang, Chunpeng; Wang, Liguo; Wu, Dayong; Chen, Hongyan; Chen, Zhong; Thomas-Ahner, Jennifer M.; Zynger, Debra L.; Eeckhoute, Jérôme; Yu, Jindan; Luo, Jun; Brown, Myles; Clinton, Steven K.; Nephew, Kenneth; Huang, Tim H M; Li, Wei; Wang, Qianben.

In: Cancer Research, Vol. 71, No. 21, 01.11.2011, p. 6738-6748.

Research output: Contribution to journalArticle

Zhang, C, Wang, L, Wu, D, Chen, H, Chen, Z, Thomas-Ahner, JM, Zynger, DL, Eeckhoute, J, Yu, J, Luo, J, Brown, M, Clinton, SK, Nephew, K, Huang, THM, Li, W & Wang, Q 2011, 'Definition of a FoxA1 cistrome that is crucial for G 1 to S-phase cell-cycle transit in castration-resistant prostate cancer', Cancer Research, vol. 71, no. 21, pp. 6738-6748. https://doi.org/10.1158/0008-5472.CAN-11-1882
Zhang, Chunpeng ; Wang, Liguo ; Wu, Dayong ; Chen, Hongyan ; Chen, Zhong ; Thomas-Ahner, Jennifer M. ; Zynger, Debra L. ; Eeckhoute, Jérôme ; Yu, Jindan ; Luo, Jun ; Brown, Myles ; Clinton, Steven K. ; Nephew, Kenneth ; Huang, Tim H M ; Li, Wei ; Wang, Qianben. / Definition of a FoxA1 cistrome that is crucial for G 1 to S-phase cell-cycle transit in castration-resistant prostate cancer. In: Cancer Research. 2011 ; Vol. 71, No. 21. pp. 6738-6748.
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