Document Detail

Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor.
MedLine Citation:
PMID:  7774807     Owner:  NLM     Status:  MEDLINE    
The insulin gene is one of the best paradigms of tissue-specific gene expression. It is developmentally regulated and is expressed exclusively in the pancreatic beta-cell. This restricted expression is directed by a tissue-specific enhancer, within the promoter, which contains an E-box sequence. The insulin E-box binds an islet-specific protein complex, termed 3a1. E-boxes bind proteins belonging to the basic helix-loop-helix (bHLH) family of transcription factors. The bHLH proteins function as potent transcriptional activators of tissue-specific genes by forming heterodimers between ubiquitous and cell-restricted family members. In addition, the cell-restricted bHLH members play an important role in specifying cell fate. To isolate the tissue-specific bHLH factor controlling insulin gene expression and study its role in islet cell differentiation, a modified yeast two-hybrid system was utilized to clone a novel bHLH factor, BETA2 (beta-cell E-box trans-activator 2), from a hamster insulin tumor (HIT) cell cDNA library. Northern analysis demonstrates that high-level expression of the BETA2 gene is restricted to pancreatic alpha- and beta-cell lines. As expected of tissue-specific bHLH members, BETA2 binds to the insulin E-box sequence with high affinity as a heterodimer with the ubiquitous bHLH factor E47. More importantly, antibody supershift experiments clearly show that BETA2 is a component of the native insulin E-box-binding complex. Transient transfection assays demonstrate that the BETA2/E47 heterodimer synergistically interacts with a neighboring beta-cell-specific complex to activate an insulin enhancer. In contrast, other bHLH factors such as MyoD and E47, which can bind to the insulin E-box with high affinity, fail to do so. Thus, a unique, cooperative interaction is the basis by which the insulin E-box enhancer discriminates between various bHLH factors to achieve tissue-specific activation of the insulin gene.
F J Naya; C M Stellrecht; M J Tsai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Genes & development     Volume:  9     ISSN:  0890-9369     ISO Abbreviation:  Genes Dev.     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-07-07     Completed Date:  1995-07-07     Revised Date:  2009-11-23    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1009-19     Citation Subset:  IM    
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
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MeSH Terms
Amino Acid Sequence
Base Sequence
DNA-Binding Proteins / genetics*,  metabolism
Gene Expression Regulation*
Helix-Loop-Helix Motifs*
Insulin / biosynthesis*,  genetics
Islets of Langerhans / cytology,  metabolism*
Molecular Sequence Data
Protein Binding
RNA, Messenger / biosynthesis
Recombinant Proteins / biosynthesis
Regulatory Sequences, Nucleic Acid
Selection, Genetic
Sequence Analysis, DNA
Sequence Homology, Amino Acid
TCF Transcription Factors
Trans-Activators / genetics*
Transcription Factors*
Transcription, Genetic
Yeasts / genetics
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/RNA, Messenger; 0/Recombinant Proteins; 0/TCF Transcription Factors; 0/Trans-Activators; 0/Transcription Factors; 0/transcription factor 7-like 1 protein; 11061-68-0/Insulin

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