Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 23, Issue 8, Pages 2720-2732Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.23.8.2720-2732.2003
Keywords
-
Categories
Funding
- Telethon [GGP04245, E.0613] Funding Source: Medline
Ask authors/readers for more resources
HMGI-Y is an architectural transcription factor that regulates gene expression in vivo by controlling the formation of stereospecific multiprotein complexes on the AT-rich regions of certain gene promoters. Recently, we demonstrated that HMGI-Y is required for proper transcription of the insulin receptor (IR) gene. Here we provide evidence that transcriptional activation of the human IR promoter requires the assembly of a transcriptionally active multiprotein-DNA complex which includes, in addition to HMGI-Y, the ubiquitously expressed transcription factor Sp1 and the CCAAT-enhancer binding protein beta (C/EBPbeta). Functional integrity of this nucleoprotein complex is required for full transactivation of the IR gene by Sp1 and C/EBPbeta in cells readily expressing IRs. We show that HMGI-Y physically interacts with Sp1 and C/EBPO and facilitates the binding of both factors to the IR promoter in vitro. Furthermore, HMGI-Y is needed for transcriptional synergism between these factors in vivo. Repression of HMGI-Y function adversely affects both Sp1- and C/EBPbeta-induced transactivation of the IR promoter. Together, these findings demonstrate that HMGI-Y plays significant molecular roles in the transcriptional activities of these factors in the context of the IR gene and provide concordant support for the hypothesis that, in affected individuals, a putative defect in these nuclear proteins may cause decreased IR expression with subsequent impairment of insulin signaling and action.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available