FoxG1, a member of the forkhead family, is a corepressor of the androgen receptor.
The androgen receptor (AR) is a ligand-dependent transcriptional regulator which belongs to the nuclear receptor superfamily. The basal transcriptional activity of the androgen receptor is regulated by interaction with coactivator or corepressor proteins. The exact mechanism whereby comodulators influence target gene transcription is only partially understood, especially for corepressors. Whereas several coactivators are described for the AR, only a few corepressors are known. Here, we describe the discovery of a new androgen receptor corepressor, FoxG1, which belongs to the forkhead family. By using a fragment of the AR (aa 325-919) as bait in a yeast two hybrid screen, the C-terminal region (aa 175-489) of FoxG1 (also known as BF1), was identified as AR-interacting protein. Binding of AR to the FoxG1 fragment was verified by one- and two-hybrid assays, and pull-down experiments. In addition, we show that the full-length form of FoxG1 functions as a strong corepressor in the AR-mediated transactivation. The FoxG1 expression profile in adult individuals is restricted to brain and testis in human and decreases during aging in the rodent brain. Both AR and FoxG1 expression are developmentally regulated. Besides its reported role in neurogenesis, the strong expression of FoxG1 in AR-abundant areas of the adult brain suggests possible involvement in neuroendocrine regulation. Taken together, the data presented suggest that, in addition to repression of transcription by direct binding to DNA, FoxG1 may interact with AR in vivo, thereby targeting its repressor function specifically to sex hormone signaling.
Obendorf
Maik
M
Schering AG/Jenapharm GmbH&Co.KG, CRBA G&A, Otto-Schott-Str. 15, D-07745 Jena, Germany. Maik.Obendorf@bayerhealthcare.com
Meyer
Rene
R
Henning
Konstanze
K
Mitev
Youri A
YA
Schröder
Jens
J
Patchev
Vladimir K
VK
Wolf
Siegmund S
SS
D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D051858:Forkhead Transcription Factors / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution; D000071161:Forkhead Box Protein O1
D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011980:Receptors, Progesterone; D012097:Repressor Proteins; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1