NDLI: Islet β-Cell-Specific MafA Transcription Requires the 5′-Flanking Conserved Region 3 Control Domain▿

Content Provider	PubMed Central
Author	Raum, Jeffrey C. Hunter, Chad S. Artner, Isabella Henderson, Eva Guo, Min Elghazi, Lynda Beatriz, Sosa-pineda Ogihara, Takeshi Mirmira, Raghavendra G. Lori, Sussel Stein, Roland
Copyright Year	2010
Abstract	MafA is a key transcriptional activator of islet β cells, and its exclusive expression within β cells of the developing and adult pancreas is distinct among pancreatic regulators. Region 3 (base pairs −8118 to −7750 relative to the transcription start site), one of six conserved 5′ cis domains of the MafA promoter, is capable of directing β-cell-line-selective expression. Transgenic reporters of region 3 alone (R3), sequences spanning regions 1 to 6 (R1-6; base pairs −10428 to +230), and R1-6 lacking R3 (R1-6ΔR3) were generated. Only the R1-6 transgene was active in MafA+ insulin+ cells during development and in adult cells. R1-6 also mediated glucose-induced MafA expression. Conversely, pancreatic expression was not observed with the R3 or R1-6ΔR3 line, although much of the nonpancreatic expression pattern was shared between the R1-6 and R1-6ΔR3 lines. Further support for the importance of R3 was also shown, as the islet regulators Nkx6.1 and Pax6, but not NeuroD1, activated MafA in gel shift, chromatin immunoprecipitation (ChIP), and transfection assays and in vivo mouse knockout models. Lastly, ChIP demonstrated that Pax6 and Pdx-1 also bound to R1 and R6, potentially functioning in pancreatic and nonpancreatic expression. These data highlight the nature of the cis- and trans-acting factors controlling the β-cell-specific expression of MafA.
Related Links	http://dx.doi.org/10.1128/MCB.01396-09
Ending Page	4244
Page Count	11
Starting Page	4234
File Format	PDF
ISSN	10985549
e-ISSN	10985549
Journal	Molecular and Cellular Biology
Issue Number	17
Volume Number	30
Language	English
Publisher	American Society for Microbiology (ASM)
Publisher Date	2010-09-01
Access Restriction	Open
Rights Holder	American Society for Microbiology (ASM)
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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