Unknown

Dataset Information

0

Identification of an INSM1-binding site in the insulin promoter: negative regulation of the insulin gene transcription.


ABSTRACT: In this study, an insulinoma-associated antigen-1 (INSM1)-binding site in the proximal promoter sequence of the insulin gene was identified. The co-transfection of INSM1 with rat insulin I/II promoter-driven reporter genes exhibited a 40-50% inhibitory effect on the reporter activity. Mutational experiments were performed by introducing a substitution, GG to AT, into the INSM1 core binding site of the rat insulin I/II promoters. The mutated insulin promoter exhibited a three- to 20-fold increase in the promoter activity over the wild-type promoter in several insulinoma cell lines. Moreover, INSM1 overexpression exhibited no inhibitory effect on the mutated insulin promoter. Chromatin immunoprecipitation assays using beta TC-1, mouse fetal pancreas, and Ad-INSM1-transduced human islets demonstrated that INSM1 occupies the endogenous insulin promoter sequence containing the INSM1-binding site in vivo. The binding of the INSM1 to the insulin promoter could suppress approximately 50% of insulin message in human islets. The mechanism for transcriptional repression of the insulin gene by INSM1 is mediated through the recruitment of cyclin D1 and histone deacetylase-3 to the insulin promoter. Anti-INSM1 or anti-cyclin D1 morpholino treatment of fetal mouse pancreas enhances the insulin promoter activity. These data strongly support the view that INSM1 is a new zinc-finger transcription factor that modulates insulin gene transcription during early pancreas development.

SUBMITTER: Wang HW 

PROVIDER: S-EPMC2529182 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Identification of an INSM1-binding site in the insulin promoter: negative regulation of the insulin gene transcription.

Wang Hong-Wei HW   Muguira Michelle M   Liu Wei-Dong WD   Zhang Tao T   Chen Chiachen C   Aucoin Rebecca R   Breslin Mary B MB   Lan Michael S MS  

The Journal of endocrinology 20080416 1


In this study, an insulinoma-associated antigen-1 (INSM1)-binding site in the proximal promoter sequence of the insulin gene was identified. The co-transfection of INSM1 with rat insulin I/II promoter-driven reporter genes exhibited a 40-50% inhibitory effect on the reporter activity. Mutational experiments were performed by introducing a substitution, GG to AT, into the INSM1 core binding site of the rat insulin I/II promoters. The mutated insulin promoter exhibited a three- to 20-fold increase  ...[more]

Similar Datasets

| S-EPMC2841680 | biostudies-literature
| S-EPMC2756239 | biostudies-literature
| S-EPMC2629780 | biostudies-literature
| S-EPMC168956 | biostudies-literature
| S-EPMC2582919 | biostudies-literature
| S-EPMC3246418 | biostudies-literature
| S-EPMC3170328 | biostudies-literature
| S-EPMC7307170 | biostudies-literature
| S-EPMC3389974 | biostudies-literature
| S-EPMC6826907 | biostudies-literature