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Islet {beta}-cell-specific MafA transcription requires the 5'-flanking conserved Region 3 control domain.

Raum, Jeffrey C; Hunter, Chad S; Artner, Isabella LU ; Henderson, Eva; Guo, Min; Elghazi, Lynda; Sosa-Pineda, Beatriz; Ogihara, Takeshi; Mirmira, Raghavendra G and Sussel, Lori, et al. (2010) In Molecular and Cellular Biology 30(17). p.4234-4244
Abstract
MafA is a key transcriptional activator of islet beta cells and its exclusive expression within beta cells of the developing and adult pancreas is distinct amongst pancreatic regulators. Region 3 (base pairs -8118/-7750 relative to the transcription start site), one of six conserved 5' cis-domains of the MafA promoter, is capable of directing beta-cell-line-selective expression. Transgenic reporters of Region 3 alone (R3), sequences spanning Regions 1-6 (R1-6; base pairs -10428/+230), and R1-6 lacking Region 3 (R1-6(DeltaR3)) were generated. Only the R1-6 transgene was active in MafA(+) insulin(+) cells during development and in adults. R1-6 also mediated glucose-induced MafA expression. Conversely, pancreatic expression was not observed... (More)
MafA is a key transcriptional activator of islet beta cells and its exclusive expression within beta cells of the developing and adult pancreas is distinct amongst pancreatic regulators. Region 3 (base pairs -8118/-7750 relative to the transcription start site), one of six conserved 5' cis-domains of the MafA promoter, is capable of directing beta-cell-line-selective expression. Transgenic reporters of Region 3 alone (R3), sequences spanning Regions 1-6 (R1-6; base pairs -10428/+230), and R1-6 lacking Region 3 (R1-6(DeltaR3)) were generated. Only the R1-6 transgene was active in MafA(+) insulin(+) cells during development and in adults. R1-6 also mediated glucose-induced MafA expression. Conversely, pancreatic expression was not observed with the R3 or R1-6(DeltaR3) lines, although much of the non-pancreatic expression pattern was shared between the R1-6 and R1-6(DeltaR3) lines. Further support for the importance of Region 3 was shown as the islet regulators Nkx6.1 and Pax6, but not NeuroD1 activated MafA using gel shift, chromatin immunoprecipitation (ChIP), transfection assays, and in vivo mouse knockout models. Lastly ChIP demonstrated that Pax6 and Pdx-1 bound also to Regions 1 and 6, potentially functioning in pancreatic and non-pancreatic expression. These data highlight the nature of the cis- and trans-acting factors controlling the beta-3cell-specific expression of MafA. (Less)
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Contribution to journal
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published
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Molecular and Cellular Biology
volume
30
issue
17
pages
4234 - 4244
publisher
American Society for Microbiology
external identifiers
  • wos:000280762900012
  • pmid:20584984
  • scopus:77956636575
ISSN
0270-7306
DOI
10.1128/MCB.01396-09
language
English
LU publication?
yes
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743e9287-f328-4a00-9f48-2d54da350758 (old id 1625633)
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http://www.ncbi.nlm.nih.gov/pubmed/20584984?dopt=Abstract
date added to LUP
2010-07-05 21:44:11
date last changed
2018-05-29 12:09:27
@article{743e9287-f328-4a00-9f48-2d54da350758,
  abstract     = {MafA is a key transcriptional activator of islet beta cells and its exclusive expression within beta cells of the developing and adult pancreas is distinct amongst pancreatic regulators. Region 3 (base pairs -8118/-7750 relative to the transcription start site), one of six conserved 5' cis-domains of the MafA promoter, is capable of directing beta-cell-line-selective expression. Transgenic reporters of Region 3 alone (R3), sequences spanning Regions 1-6 (R1-6; base pairs -10428/+230), and R1-6 lacking Region 3 (R1-6(DeltaR3)) were generated. Only the R1-6 transgene was active in MafA(+) insulin(+) cells during development and in adults. R1-6 also mediated glucose-induced MafA expression. Conversely, pancreatic expression was not observed with the R3 or R1-6(DeltaR3) lines, although much of the non-pancreatic expression pattern was shared between the R1-6 and R1-6(DeltaR3) lines. Further support for the importance of Region 3 was shown as the islet regulators Nkx6.1 and Pax6, but not NeuroD1 activated MafA using gel shift, chromatin immunoprecipitation (ChIP), transfection assays, and in vivo mouse knockout models. Lastly ChIP demonstrated that Pax6 and Pdx-1 bound also to Regions 1 and 6, potentially functioning in pancreatic and non-pancreatic expression. These data highlight the nature of the cis- and trans-acting factors controlling the beta-3cell-specific expression of MafA.},
  author       = {Raum, Jeffrey C and Hunter, Chad S and Artner, Isabella and Henderson, Eva and Guo, Min and Elghazi, Lynda and Sosa-Pineda, Beatriz and Ogihara, Takeshi and Mirmira, Raghavendra G and Sussel, Lori and Stein, Roland},
  issn         = {0270-7306},
  language     = {eng},
  number       = {17},
  pages        = {4234--4244},
  publisher    = {American Society for Microbiology},
  series       = {Molecular and Cellular Biology},
  title        = {Islet {beta}-cell-specific MafA transcription requires the 5'-flanking conserved Region 3 control domain.},
  url          = {http://dx.doi.org/10.1128/MCB.01396-09},
  volume       = {30},
  year         = {2010},
}