Journal
FEBS LETTERS
Volume 581, Issue 5, Pages 949-954Publisher
WILEY
DOI: 10.1016/j.febslet.2007.01.087
Keywords
neurogenin 3; insulinoma-associated 1; CREB-binding protein; histone acetylation; transcriptional activation
Funding
- NIDDK NIH HHS [DK61436, R01 DK061436] Funding Source: Medline
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INSM1 is a downstream target gene of neurogenin 3 (ngn3). A promoter construct containing the -426/+40 bp region transiently co-transfected into NIH-3T3 cells with a ngn3 expression plasmid resulted in a 12-fold increase in promoter activity. The ngn3/E47 heterodimer selectively binds and activates the E-box3 of the INSM1 promoter. The endogenous ngn3 and CREB-binding protein (CBP) co-activator occupy the INSM1 promoter, resulting in hyper-acetylation of histone H3/H4 chromatin in a human neuroblastoma cell line, IMR32. Additionally, adenoviral ngn3 can induce endogenous INSM-1 expression in pancreatic ductal carcinoma-1 cells through the recruitment of CBP to the INSM1 promoter and increase the acetylation of the INSM1 promoter region. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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