A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription.

Mol Cell Biol 2003 Apr;23(8):2720-32

Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università degli Studi di Catanzaro Magna Graecia, 88100 Catanzaro, Italy.

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/EBP beta). Functional integrity of this nucleoprotein complex is required for full transactivation of the IR gene by Sp1 and C/EBP beta in cells readily expressing IRs. We show that HMGI-Y physically interacts with Sp1 and C/EBP beta 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/EBP beta-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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC152545PMC
http://dx.doi.org/10.1128/mcb.23.8.2720-2732.2003DOI Listing
April 2003
3 Reads

Publication Analysis

Top Keywords

c/ebp beta
16
sp1 c/ebp
12
insulin receptor
8
gene provide
8
receptor gene
8
hmgi-y
8
transcription factor
8
nucleoprotein complex
8
gene
6
beta
5
c/ebp
5
physically interacts
4
hmgi-y physically
4
expressing irs
4
beta cells
4
cells expressing
4
irs hmgi-y
4
binding factors
4
vitro hmgi-y
4
hmgi-y needed
4

References

(Supplied by CrossRef)

Similar Publications