A novel estrogen receptor alpha-associated protein, template-activating factor Ibeta, inhibits acetylation and transactivation.
Estrogen receptor-alpha (ERalpha) functions as a ligand-activated transcription factor that alters expression of estrogen-responsive genes in target cells. Numerous regulatory proteins interact with ERalpha to influence estrogen-mediated transactivation. We have identified a novel coregulatory protein, template-activating factor-Ibeta (TAF-Ibeta), which binds to ERalpha in vitro when the receptor is not complexed with an estrogen response element. The central region of TAF-Ibeta interacts with both the DNA-binding domain and the carboxy-terminal region of ERalpha. Coimmunoprecipitation experiments demonstrate that TAF-Ibeta is associated with the unoccupied, but not the estrogen-occupied, ERalpha in MCF-7 breast cancer cells. Overexpression of TAF-Ibeta inhibits ERalpha-mediated transcription in a dose- dependent manner. TAF-Ibeta represses p300-mediated acetylation of histones and ERalpha in vitro and decreases ERalpha acetylation in vivo. TAF-Ibeta also binds to other nuclear receptor superfamily members and represses thyroid hormone receptor beta- induced transcription in transient transfection assays. Taken together, these data provide evidence that TAF-Ibeta regulates transcription of estrogen- responsive genes by modulating acetylation of histones and ERalpha and that the effects of TAF-Ibeta extend to other nuclear receptor superfamily members as well.
Loven
Margaret A
MA
Department of Molecular and Integrative Physiology, University of Illinois, Urbana, Illinois 61801, USA.
Muster
Nemone
N
Yates
John R
JR
Nardulli
Ann M
AM
D000107:Acetylation; D001943:Breast Neoplasms; D002868:Chromosomal Proteins, Non-Histone / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha; D005786:Gene Expression Regulation / Q000502:physiology*; D056488:Histone Chaperones; D006801:Humans; D012516:Osteosarcoma; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D056488:Histone Chaperones; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; C513473:SET protein, human; D014157:Transcription Factors