Cellular context of coregulator and adaptor proteins regulates human adenovirus 5 early region 1A-dependent gene activation by the thyroid hormone receptor.
In mammalian cells, the human adenovirus type 5 early region 1A (E1A) oncoprotein functions as a thyroid hormone (TH)-dependent activator of the thyroid hormone receptor (TR). Interestingly, in the cellular context of the yeast Saccharomyces cerevisiae, E1A acts as a TR-specific constitutive coactivator that is down-regulated by TH. TH reduces the interaction of E1A with the TR in yeast but not HeLa cells. The N-terminal 82 amino acids of E1A are sufficient for coactivation in yeast and residues 4-29 are essential. In yeast, expression of the nuclear receptor corepressor (N-CoR) could down-regulate constitutive transcriptional activation of the TR by E1A, whereas expression of the glucocorticoid receptor interacting protein 1 (GRIP-1) coactivator reconstituted the E1A-induced pattern of enhanced TH-dependent gene activation by TR observed in mammalian cells. We further show that the mating type switching gene (SWI)/sucrose nonfermenting (SNF) gene chromatin remodeling complex is required for both TH/GRIP-1- and E1A-dependent coactivator function, whereas the general control nonrepressed protein (GCN5)/alteration/deficiency in activation protein (ADA2) components of the SPT, ADA, GCN5, acetylation (SAGA) transcriptional adaptor complex are required for TH/GRIP-1, but not E1A-dependent activation of the TR. Taken together, these studies demonstrate that the novel TR-specific coactivator function of E1A in yeast depends on the SWI/SNF chromatin remodeling complex and can be further influenced by changes in the cellular complement of transcriptional coregulatory proteins.
Meng
Xianwang
X
Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Endocrine Division, University of Toronto Medical School, Toronto, Ontario, Canada M5G 1X5.
Yang
Yong-Fan
YF
Cao
Xiemin
X
Govindan
Manjapra V
MV
Shuen
Michael
M
Hollenberg
Anthony N
AN
Mymryk
Joe S
JS
Walfish
Paul G
PG
D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D051958:Nuclear Receptor Coactivator 2; D011494:Protein Kinases / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D000099224:p300-CBP-Associated Factor
D017500:Adenovirus E1A Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D051958:Nuclear Receptor Coactivator 2; D011494:Protein Kinases; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C090575:ADA2 protein, S cerevisiae; C498001:NCOA2 protein, human; C539127:NCOR1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor