期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 33, 页码 22612-22619出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M802902200
关键词
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资金
- NIDDK NIH HHS [P60 DK20593, P01 DK42502, 5T32 DK07563-20, DK50203] Funding Source: Medline
Pancreatic-duodenal homeobox factor-1 (Pdx1) is highly enriched in islet beta cells and integral to proper cell development and adult function. Of the four conserved 5'-flanking sequence blocks that contribute to transcription in vivo, Area II (mouse base pairs -2153/-1923) represents the only mammalian specific control domain. Here we demonstrate that regulation of beta-cell-enriched Pdx1 expression by the MafA and MafB transcription factors is exclusively through Area II. Thus, these factors were found to specifically activate through Area II in cell line transfection-based assays, and MafA, which is uniquely expressed in adult islet beta cells was only bound to this region in quantitative chromatin immuno-precipitation studies. MafA and MafB are produced in beta cells during development and were both bound to Area II at embryonic day 18.5. Expression of a transgene driven by Pdx1 Areas I and II was also severely compromised during insulin (+) cell formation in MafB (-)/(-)mice, consistent with the importance of this large Maf in beta-cell production and Pdx1 expression. These findings illustrate the significance of large Maf proteins to Pdx1 expression in beta cells, and in particular MafB during pancreatic development.
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