p300 cooperates with Smad3/4 and Runx3 in TGFbeta1-induced IgA isotype expression.
We have shown previously that Smad3 and Smad4 mediate TGF-beta1-induced IgA expression. In the present study, we examined the involvement of Runx3 in this process. Overexpression of Runx3 in mice increased germ-line alpha (GLalpha) transcription, and transcription was further augmented when B lymphoma and LPS-activated murine spleen cells were co-transfected with Smad3/4. Overexpression of Runx3 and Smad3/4 increased IgA secretion by both cell types in response to TGF-beta1. p300, which has histone acetyltransferase activity, further augmented TGF-beta1-induced GLalpha transcription promoted by Smad3/4 and Runx3. These observations were confirmed by examining the influence of Smad3/4, Runx3 and p300 on the expression of endogenous GLalpha and post-switch alpha transcripts.E1A, an inhibitor of p300, blocked both GLalpha promoter activity and the enhancement of endogenous GLalpha transcription by Smad3/4 and Runx3. We conclude that p300 cooperates with Smad3/4 and Runx3 in stimulating TGF-beta1-induced GLalpha transcription and subsequent IgA isotype expression, while E1A inhibits these cooperative effects.
Park
Seok-Rae
SR
Department of Microbiology, College of Natural Sciences, Kangwon National University, Chunchon, S. Korea.
Lee
Eun-Kyoung
EK
Kim
Byung-Chul
BC
Kim
Pyeung-Hyeun
PH
D017500:Adenovirus E1A Proteins / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000502:physiology*; D050881:E1A-Associated p300 Protein; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000235:genetics*; D017578:Immunoglobulin Class Switching; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D017500:Adenovirus E1A Proteins; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D007070:Immunoglobulin A; D009687:Nuclear Proteins; C493730:Runx3 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse