Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene.
Androgen receptor (AR) induced precocious myogenesis in culture and myogenic specified gene activity. Increased levels of AR expression in replicating C2C12 myoblasts stimulated fusion into post-differentiated multinucleated myotubes and the appearance of skeletal alpha-actin transcripts, even in the absence of ligand. Furthermore, AR activated the skeletal alpha-actin promoter, which lacks GRE sites, in co-transfected C2C12 cells. AR co-activation of the skeletal alpha-actin promoter required co-expressed full-length serum response factor (SRF). In vitro, AR associated with SRF and was recruited by SRF to a alpha-actin promoter SRF binding site. Our data suggest that AR is capable of activating myogenic genes devoid of consensus AR binding sites via its recruitment by the myogenic enriched transcription factor, SRF.
Vlahopoulos
Spiros
S
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Zimmer
Warren E
WE
Jenster
Guido
G
Belaguli
Narasimhaswamy S
NS
Balk
Steven P
SP
Brinkmann
Albert O
AO
Lanz
Rainer B
RB
Zoumpourlis
Vassilis C
VC
Schwartz
Robert J
RJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000166:cytology; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000737:chemistry* / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection
D000199:Actins; D017931:DNA Primers; D008024:Ligands; D012333:RNA, Messenger; D011944:Receptors, Androgen; D026362:Serum Response Factor; D004247:DNA; D005982:Glutathione Transferase