Unknown,Transcriptomics,Genomics,Proteomics

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Pioneer factor FOXA1 defines GATA2- and AR-mediated transcriptional program in prostate cancer [ChIP-Seq]


ABSTRACT: AR is tightly regulated by many transcriptional cofactors, including key pioneer factor such as FOXA1 and GATA2. While FOXA1 was recently shown to be able to redistribute AR across the genome, how GATA2 regulates AR cistrome has not been carefully investigated. Here, we report that, unlike FOXA1, GATA2 is unable to reprogram AR, but instead it enhances AR program by inducing AR expression and augmenting AR co-occupancy, thereby acting as a pure AR coactivator, rather than a pioneer factor. On the other hand, AR co-occupancy enhances both GATA2 and FOXA1 binding on the chromatin, forming a positive feedback loop. Importantly, we found that FOXA1 is also capable of reprogramming GATA2 by recruiting GATA2 from GATA motif to FKHD-containing regions, being analogous to its pioneering effect on AR signaling. By contrast, GATA2 simply acts as a co-activator of FOXA1 with a lack of pioneering ability. ChIP_Seq examination of AR, FoxA1 and GATA2 binding sites in LNCaP and DU145 cells

ORGANISM(S): Homo sapiens

SUBMITTER: Jindan Yu 

PROVIDER: E-GEOD-69043 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

FOXA1 acts upstream of GATA2 and AR in hormonal regulation of gene expression.

Zhao J C JC   Fong K-W KW   Jin H-J HJ   Yang Y A YA   Kim J J   Yu J J  

Oncogene 20160111 33


Hormonal regulation of gene expression by androgen receptor (AR) is tightly controlled by many transcriptional cofactors, including pioneer factors FOXA1 and GATA2, which, however, exhibit distinct expression patterns and functional roles in prostate cancer. Here, we examined how FOXA1, GATA2 and AR crosstalk and regulate hormone-dependent gene expression in prostate cancer cells. Chromatin immunoprecipitation sequencing analysis revealed that FOXA1 reprograms both AR and GATA2 cistrome by prefe  ...[more]

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