title: Expression of insulinoma-associated 2 (INSM2) in pancreatic islet cells is regulated by the transcription factors Ngn3 and NeuroD1.
abstract: The insulinoma-associated 2 (Insm2) gene is a member of the Snail/Gfi1/Insm1 transcriptional repressor superfamily. However, little is known about how the expression of human INSM2 or mouse Insm2 in neuroendocrine tissues is regulated. Here we report the expression of INSM2/Insm2 in human fetal pancreas and mouse embryos, as well as adult pancreatic islets, and its regulation by two major islet transcription factors. Mutagenesis and chromatin immunoprecipitation analysis demonstrated that the proximal E-boxes of the mouse Insm2 promoter are direct targets of neurogenin 3 and neurogenic differentiation 1 (NeuroD1). Furthermore, we found that endogenous Insm2 expression was activated in Ngn3/NeuroD1-transduced pancreatic epithelial duct cells. Our results suggest that Insm2 plays an important role in the differentiation cascade of Ngn3/NeuroD1 signaling in pancreatic islets.
authors.affiliation: National Institute of Dental and Craniofacial Research/National Institutes of Health, Bethesda, Maryland 20892, USA. tcai@mail.nih.gov
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Rennian
authors.initials: R
authors.lastname: Wang
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.forename: Yuhui
authors.initials: Y
authors.lastname: You
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lan
authors.forename: Abner L
authors.initials: AL
authors.lastname: Notkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006367:HeLa Cells; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010179:Pancreas / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C501008:Neurod1 protein, mouse; C407737:Neurog3 protein, mouse