Home LiteratureArticle Details
PMID: 14973194 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The MafA transcription factor appears to be responsible for tissue-specific expression of insulin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 9 ·2004-03-02 ·Pages 2930-3

Matsuoka TA, Artner I, Henderson E, Means A, Sander M, Stein R

Abstract

Insulin gene expression is regulated by several islet-enriched transcription factors. However, MafA is the only beta cell-specific activator. Here, we show that MafA selectively induces endogenous insulin transcription in non-beta cells. MafA was also first detected in the insulin-producing cells formed during the second and predominant phase of beta cell differentiation, and absent in the few insulin-positive cells found in Nkx6.1(-/-) pancreata, which lack the majority of second-phase beta cells. These results demonstrate that MafA is a potent insulin activator that is likely to function downstream of Nkx6.1 during islet insulin-producing cell development.

MeSH Terms
Animals Base Sequence Cell Line DNA Primers Gene Expression Regulation/genetics Humans Immunohistochemistry Insulin/biosynthesis,genetics Islets of Langerhans/physiology Lectins, C-Type Maf Transcription Factors, Large Mice Molecular Sequence Data Organ Specificity Rats Receptors, Immunologic Recombinant Proteins/biosynthesis Trans-Activators/metabolism Transcription Factors/metabolism Transfection
Chemicals
DNA Primers Insulin KLRG1 protein, human Lectins, C-Type Maf Transcription Factors, Large Mafa protein, mouse Receptors, Immunologic Recombinant Proteins Trans-Activators Transcription Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Matsuoka Taka-aki
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 723 Light Hall, Nashville, TN 37232, USA.
Artner Isabella
Henderson Eva
Means Anna
Sander Maike
Stein Roland
References (30)
30 references, click to expand
  1. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus.
    Nat Genet. 1999 Nov;23(3):323-8 PMID: 10545951
  2. Rat endocrine pancreatic development in relation to two homeobox gene products (Pdx-1 and Nkx 6.1).
    J Histochem Cytochem. 1998 Jun;46(6):707-15 PMID: 9603781
  3. The RIPE3b1 activator of the insulin gene is composed of a protein(s) of approximately 43 kDa, whose DNA binding activity is inhibited by protein phosphatase treatment.
    J Biol Chem. 2000 Apr 7;275(14):10532-7 PMID: 10744746
  4. Regulation of insulin gene transcription.
    Semin Cell Dev Biol. 2000 Aug;11(4):227-33 PMID: 10966856
  5. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas.
    Development. 2000 Dec;127(24):5533-40 PMID: 11076772
  6. Interaction of Maf transcription factors with Pax-6 results in synergistic activation of the glucagon promoter.
    J Biol Chem. 2001 Sep 21;276(38):35751-60 PMID: 11457839
  7. PAX6 mutation as a genetic factor common to aniridia and glucose intolerance.
    Diabetes. 2002 Jan;51(1):224-30 PMID: 11756345
  8. Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA.
    Proc Natl Acad Sci U S A. 2002 May 14;99(10):6737-42 PMID: 12011435
  9. MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene.
    J Biol Chem. 2002 Dec 20;277(51):49903-10 PMID: 12368292
  10. Gene expression cascades in pancreatic development.
    Mech Dev. 2003 Jan;120(1):65-80 PMID: 12490297
  11. The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression.
    J Biol Chem. 2003 Apr 4;278(14):12263-70 PMID: 12551916
  12. Members of the large Maf transcription family regulate insulin gene transcription in islet beta cells.
    Mol Cell Biol. 2003 Sep;23(17):6049-62 PMID: 12917329
  13. Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):9037-41 PMID: 2848253
  14. Comparison of cytokine effects on mouse pancreatic alpha-cell and beta-cell lines. Viability, secretory function, and MHC antigen expression.
    Diabetes. 1990 Apr;39(4):415-25 PMID: 2108069
  15. Cell-specific and ubiquitous factors are responsible for the enhancer activity of the rat insulin II gene.
    J Biol Chem. 1991 Sep 5;266(25):16708-14 PMID: 1885600
  16. Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo.
    Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):527-31 PMID: 8421685
  17. IPF1, a homeodomain-containing transactivator of the insulin gene.
    EMBO J. 1993 Nov;12(11):4251-9 PMID: 7901001
  18. Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun.
    Mol Cell Biol. 1994 Jan;14(1):700-12 PMID: 8264639
  19. Insulin-promoter-factor 1 is required for pancreas development in mice.
    Nature. 1994 Oct 13;371(6498):606-9 PMID: 7935793
  20. Beta cells arise from glucose transporter type 2 (Glut2)-expressing epithelial cells of the developing rat pancreas.
    Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9559-63 PMID: 7937805
  21. Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny.
    Development. 1995 Jan;121(1):11-8 PMID: 7867492
  22. Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor.
    Genes Dev. 1995 Apr 15;9(8):1009-19 PMID: 7774807
  23. The role of the insulin control element and RIPE3b1 activators in glucose-stimulated transcription of the insulin gene.
    Mol Endocrinol. 1995 Nov;9(11):1468-76 PMID: 8584024
  24. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum.
    Development. 1996 Mar;122(3):983-95 PMID: 8631275
  25. The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice.
    Development. 1996 May;122(5):1409-16 PMID: 8625829
  26. Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas.
    Nature. 1997 May 22;387(6631):406-9 PMID: 9163426
  27. Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development.
    Genes Dev. 1997 Jul 1;11(13):1662-73 PMID: 9224716
  28. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice.
    Genes Dev. 1997 Sep 15;11(18):2323-34 PMID: 9308961
  29. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1.
    Nat Genet. 1997 Oct;17(2):138-9 PMID: 9326926
  30. neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas.
    Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1607-11 PMID: 10677506
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0306233101
Published
2004-03-02
Epub
2004-00-18
Pages
2930-3
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC365722
Subset
IM
Grants
NIDDK NIH HHS · P01 DK042502 · United States
NIDDK NIH HHS · P60 DK020593 · United States
NIDDK NIH HHS · P01 DK42502 · United States
NIDDK NIH HHS · P60 DK20593 · United States
External Links
PubMed source DOI: 10.1073/pnas.0306233101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2