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The minimal promoter region of the dense-core vesicle protein IA-2: transcriptional regulation by CREB.
The minimal promoter region of the dense-core vesicle protein IA-2: transcriptional regulation by CREB.
- Source :
-
Acta diabetologica [Acta Diabetol] 2015 Jun; Vol. 52 (3), pp. 573-80. Date of Electronic Publication: 2014 Dec 21. - Publication Year :
- 2015
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Abstract
- Aims: IA-2 is a transmembrane protein found in the dense-core vesicles (DCV) of neuroendocrine cells and one of the major autoantigens in type 1 diabetes. DCV are involved in the secretion of hormones (e.g., insulin) and neurotransmitters. Stimulation of pancreatic β cells with glucose upregulates the expression of IA-2 and an increase in IA-2 results in an increase in the number of DCV. Little is known, however, about the promoter region of IA-2 or the transcriptional factors that regulate the expression of this gene.<br />Methods: In the present study, we constructed eight deletion fragments from the upstream region of the IA-2 transcription start site and linked them to a luciferase reporter.<br />Results: By this approach, we have identified a short bp region (-216 to +115) that has strong promoter activity. We also identified a transcription factor, cAMP responsive element-binding protein (CREB), which binds to two CREB-related binding sites located in this region. The binding of CREB to these sites enhanced IA-2 transcription by more than fivefold. We confirmed these findings by site-directed mutagenesis, chromatin immunoprecipitation assays and RNAi inhibition.<br />Conclusion: Based on these findings, we conclude that the PKA pathway is a critical, but not the exclusive signaling pathway involved in IA-2 gene expression.<br />Competing Interests: Tao Cai, Hiroki Hirai, Huanyu Xu, and Abner Notkins declare that they have no conflict of interest.
- Subjects :
- Base Sequence
Binding Sites
CREB-Binding Protein genetics
Humans
Molecular Sequence Data
Protein Binding
Receptor-Like Protein Tyrosine Phosphatases, Class 8 metabolism
Transcription, Genetic
CREB-Binding Protein metabolism
Gene Expression Regulation
Promoter Regions, Genetic
Receptor-Like Protein Tyrosine Phosphatases, Class 8 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1432-5233
- Volume :
- 52
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Acta diabetologica
- Publication Type :
- Academic Journal
- Accession number :
- 25528004
- Full Text :
- https://doi.org/10.1007/s00592-014-0689-5