Acetylation of the BETA2 transcription factor by p300-associated factor is important in insulin gene expression.
The BETA2 transcription factor influences islet beta cell development and function. Activation of insulin gene transcription by this member of the basic helix-loop-helix gene family is mediated by p300 through the ability of this coactivator to form a functional bridge between the basal transcriptional apparatus, BETA2, and PDX-1, another key transcription factor. In this report, we examined whether BETA2-mediated stimulation was also directly influenced by the acetyltransferase activities of p300 or the p300-associated factor. BETA2 was specifically and selectively acetylated by p300-associated factor in beta cells. Sites of BETA2 acetylation were found within the loop region of the basic helix-loop-helix DNA binding/dimerization domain and a more C-terminal region involved in activation. Insulin gene transcription was decreased by blocking acetylation of BETA2 because of effects on DNA binding and activation potential. These findings suggest that acetylation of BETA2 plays a role in controlling the activation state of this islet regulatory factor.
Qiu
Yi
Y
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37215, USA.
Guo
Min
M
Huang
Suming
S
Stein
Roland
R
D000123:Acetyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D000939:Epitopes; D005982:Glutathione Transferase; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D007328:Insulin; D008239:Lysine; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C093970:NEUROD1 protein, human; C501008:Neurod1 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein