Linked Life Data

15028719

Source:http://linkedlifedata.com/resource/pubmed/id/15028719

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2004-5-17
pubmed:abstractText
Islet beta cell type-specific transcription of the insulin gene is regulated by a number of cis-acting elements found within the proximal 5'-flanking region. The control sequences conserved between mammalian insulin genes are acted upon by transcription factors, like PDX-1 and BETA-2, that are also involved in islet beta cell function and formation. In the current study, we investigated the contribution to human insulin expression of the GG2 motif found between nucleotides -145 and -140 relative to the transcription start site. Site-specific mutants were generated within GG2 that displayed a parallel increase (i.e. -144 base pair) or decrease (i.e. -141 base pair) in insulin enhancer-driven reporter and gel shift binding activity in beta cells consistent with human GG2 being under positive regulatory control. In contrast, the corresponding site in the rodent insulin gene, which only differs from the human at nucleotides -144 and -141, is negatively regulated by the Nkx2.2 transcription factor (Cissell, M. A., Zhao, L., Sussel, L., Henderson, E., and Stein, R. (2003) J. Biol. Chem. 278, 751-756). Human GG2 activator binding activity was present in nuclear extracts prepared from human islets and enriched in those from rodent beta cell lines. The human GG2 activator binding factor(s) was shown to be approximately 38-40 kDa and distinct from other size-matched islet-enriched transcription factors, including Nkx2.2, Pax-4, Cdx2/3, and Isl-1. Combined DNA chromatographic purification and mass spectrometry analysis revealed that the GG2 activator was PDX-1. These results demonstrate that the GG2 element, despite its divergence from the core homeodomain consensus binding motif, is a site for PDX-1 activation in the human insulin gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22228-35
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15028719-Amino Acid Motifs, pubmed-meshheading:15028719-Animals, pubmed-meshheading:15028719-Base Sequence, pubmed-meshheading:15028719-Binding Sites, pubmed-meshheading:15028719-Cell Nucleus, pubmed-meshheading:15028719-Chromatography, pubmed-meshheading:15028719-Conserved Sequence, pubmed-meshheading:15028719-Cricetinae, pubmed-meshheading:15028719-DNA, pubmed-meshheading:15028719-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:15028719-Enhancer Elements, Genetic, pubmed-meshheading:15028719-HeLa Cells, pubmed-meshheading:15028719-Homeodomain Proteins, pubmed-meshheading:15028719-Humans, pubmed-meshheading:15028719-Insulin, pubmed-meshheading:15028719-Islets of Langerhans, pubmed-meshheading:15028719-Mass Spectrometry, pubmed-meshheading:15028719-Mice, pubmed-meshheading:15028719-Molecular Sequence Data, pubmed-meshheading:15028719-Mutagenesis, Site-Directed, pubmed-meshheading:15028719-Mutation, pubmed-meshheading:15028719-NIH 3T3 Cells, pubmed-meshheading:15028719-Peptides, pubmed-meshheading:15028719-Protein Binding, pubmed-meshheading:15028719-Trans-Activators, pubmed-meshheading:15028719-Transcription Factors, pubmed-meshheading:15028719-Transfection
pubmed:year
2004
pubmed:articleTitle
Identification of a novel PDX-1 binding site in the human insulin gene enhancer.
pubmed:affiliation
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't