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Publication : Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs.

First Author  Pihlajamaa P Year  2014
Journal  EMBO J Volume  33
Issue  4 Pages  312-26
PubMed ID  24451200 Mgi Jnum  J:206569
Mgi Id  MGI:5551512 Doi  10.1002/embj.201385895
Citation  Pihlajamaa P, et al. (2014) Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs. EMBO J 33(4):312-26
abstractText  Androgen receptor (AR) binds male sex steroids and mediates physiological androgen actions in target tissues. ChIP-seq analyses of AR-binding events in murine prostate, kidney and epididymis show that in vivo AR cistromes and their respective androgen-dependent transcription programs are highly tissue specific mediating distinct biological pathways. This high order of tissue specificity is achieved by the use of exclusive collaborating factors in the three androgen-responsive tissues. We find two novel collaborating factors for AR signaling in vivo-Hnf4alpha (hepatocyte nuclear factor 4alpha) in mouse kidney and AP-2alpha (activating enhancer binding protein 2alpha) in mouse epididymis-that define tissue-specific AR recruitment. In mouse prostate, FoxA1 serves for the same purpose. FoxA1, Hnf4alpha and AP-2alpha motifs are over-represented within unique AR-binding loci, and the cistromes of these factors show substantial overlap with AR-binding events distinct to each tissue type. These licensing or pioneering factors are constitutively bound to chromatin and guide AR to specific genomic loci upon hormone exposure. Collectively, liganded receptor and its DNA-response elements are required but not sufficient for establishment of tissue-specific transcription programs.
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