Acetylation of steroidogenic factor 1 protein regulates its transcriptional activity and recruits the coactivator GCN5.
Steroidogenic factor-1 (SF-1) is an orphan nuclear receptor that plays an essential role in the development of the hypothalamic-pituitary-gonadal axis in both sexes. SF-1 belongs to the hormone nuclear receptor superfamily and possesses an N-terminal DNA binding domain and a C-terminal ligand binding domain. Activation function domain 2 is located C-terminal of the ligand binding domain of SF-1 and is important for the transactivation of target genes. Coactivators with histone acetyltransferase activity such as cAMP response element-binding protein-binding protein and steroid receptor coactivator 1 interact and increase SF-1-mediated transcriptional activity. In this study we demonstrate that SF-1 is acetylated in vivo. Histone acetyltransferase GCN5 acetylates SF-1 in vitro. Moreover, we found that SF-1 recruited a novel coactivator GCN5, which can be a newly identified coactivator for SF-1. Acetylation of SF-1 stimulates its transcriptional activity. Inhibition of deacetylation by trichostatin A, a histone deacetylase inhibitor, increased SF-1-mediated transactivation and stabilized and induced the nuclear export of the SF-1 protein.
Jacob
A L
AL
Department of Anatomy and Cell Biology, University of Bergen, Bergen N-5009, Norway. Anne.Jacob@pki.uib.no
Lund
J
J
Martinez
P
P
Hedin
L
L
D000107:Acetylation / Q000187:drug effects; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051717:Fushi Tarazu Transcription Factors; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D016335:Zinc Fingers; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D051717:Fushi Tarazu Transcription Factors; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D006877:Hydroxamic Acids; D008239:Lysine; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C515058:steroidogenic factor 1, mouse; C012589:trichostatin A; C501178:Gcn5l2 protein, mouse