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FHL2, a novel tissue-specific coactivator of the androgen receptor
J M Müller1, U Isele, E Metzger
1Universitäts-Frauenklinik, Abteilung Frauenheilkunde und Geburtshilfe I, Klinikum der Universität Freiburg, Breisacherstrasse 117, 79106 Freiburg, Germany.
Abstract:
The control of target gene expression by nuclear receptors requires the recruitment of multiple cofactors. However, the exact mechanisms by which nuclear receptor-cofactor interactions result in tissue-specific gene regulation are unclear. Here we characterize a novel tissue-specific coactivator for the androgen receptor (AR), which is identical to a previously reported protein FHL2/DRAL with unknown function. In the adult, FHL2 is expressed in the myocardium of the heart and in the epithelial cells of the prostate, where it colocalizes with the AR in the nucleus. FHL2 contains a strong, autonomous transactivation function and binds specifically to the AR in vitro and in vivo. In an agonist- and AF-2-dependent manner FHL2 selectively increases the transcriptional activity of the AR, but not that of any other nuclear receptor. In addition, the transcription of the prostate-specific AR target gene probasin is coactivated by FHL2. Taken together, our data demonstrate that FHL2 is the first LIM-only coactivator of the AR with a unique tissue-specific expression pattern.
Insights
Researchers identified a novel coactivator, FHL2, crucial for androgen receptor (AR) gene regulation. This protein exhibits tissue-specific expression, particularly in the prostate, enhancing AR
Area of Science:
- Molecular Biology
- Genetics
- Endocrinology
Background:
- Nuclear receptors regulate gene expression via cofactor recruitment.
- Mechanisms of tissue-specific gene regulation by nuclear receptor-cofactor interactions remain incompletely understood.
Purpose of the Study:
- To characterize a novel, tissue-specific coactivator for the androgen receptor (AR).
- To elucidate the function of FHL2/DRAL in AR-mediated gene regulation.
Main Methods:
- Characterization of FHL2 protein and its interaction with AR.
- In vitro and in vivo binding assays.
- Assessment of FHL2's effect on AR transcriptional activity and target gene (probasin) transcription.
Main Results:
- Identified FHL2 as a novel coactivator for the androgen receptor (AR).
- FHL2 displays tissue-specific expression in adult heart and prostate, colocalizing with AR.
- FHL2 possesses autonomous transactivation function, specifically enhancing AR transcriptional activity in an agonist- and AF-2-dependent manner.
Conclusions:
- FHL2 is the first identified LIM-only coactivator for the AR.
- FHL2 exhibits a unique tissue-specific expression pattern, contributing to tissue-specific AR gene regulation.
- FHL2 plays a significant role in coactivating prostate-specific AR target genes like probasin.