p300 regulates the synergy of steroidogenic factor-1 and early growth response-1 in activating luteinizing hormone-beta subunit gene.
Tight regulation of luteinizing hormone-beta subunit (LHbeta) expression is critical for differentiation and maturation of mammalian sexual organs and reproductive function. Two transcription factors, steroidogenic factor-1 (SF-1) and early growth response-1 (Egr-1), play a central role in activating LHbeta promoter, and the synergy between these two factors is essential in mediating gonadotropin-releasing hormone stimulation of LHbeta promoter. Here we demonstrate that the transcriptional co-activator p300 regulates this synergy. Overexpression of p300 results in strong stimulation of LHbeta promoter but only in the presence of both SF-1 and Egr-1, and not in the presence of other Egr proteins. Mutation of the binding sites for either SF-1 or Egr-1 completely abolishes the synergy between these two factors, as well as the influence of p300. Importantly, LHbeta promoter is precipitated using p300 antibodies in a chromatin immunoprecipitation assay with LbetaT2 gonadotropes, and this effect is enhanced by gonadotropin-releasing hormone. The influence of p300 on LHbeta promoter is potentiated by steroid receptor co-activator, as well as by E1A proteins, and attenuated by Smad nuclear interacting protein 1. Taken together, these results suggest that p300 is recruited to LHbeta promoter where it coordinates the functional synergy between SF-1 and Egr-1.
Mouillet
Jean-François
JF
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Sonnenberg-Hirche
Christina
C
Yan
Xiaomei
X
Sadovsky
Yoel
Y
D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000494:pharmacology; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004357:Drug Synergism; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D018398:Homeodomain Proteins; D007163:Immunosorbent Techniques; D047908:Intracellular Signaling Peptides and Proteins; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics*; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000494:pharmacology*; D014162:Transfection
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D037101:Luteinizing Hormone, beta Subunit; C515057:NR5A1 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C411545:SNIP1 protein, human; D054339:Steroidogenic Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA