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Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking.

Abstract：

:Androgen receptor (AR) plays a critical role in the development and progression of prostate cancer, where it is a key therapeutic target. Here we report that, in contrast to estrogen receptor transcription complexes which form within minutes and recycle hourly, the levels of regulatory regions bound by AR complexes rise over a 16 hr period and then slowly decline. AR regulation of the prostate specific antigen (PSA) gene involves both a promoter-proximal sequence as well as an enhancer approximately 4 kb upstream. Recruitment of AR and its essential coactivators at both sites creates a chromosomal loop that allows RNA polymerase II (pol II) to track from the enhancer to the promoter. Phosphorylation of the pol II C-terminal domain is required for pol II tracking but not chromosomal looping. Development of improved hormonal therapies for prostate cancer must take in account the specific spatial and temporal modes of AR-mediated gene regulation.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Wang Q,Carroll JS,Brown M

doi

10.1016/j.molcel.2005.07.018

subject

Has Abstract

pub_date

2005-09-02 00:00:00

pages

631-42

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(05)01506-6

journal_volume

19

pub_type

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