Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-11-3
pubmed:abstractText
Mammalian alphaB-crystallin is highly expressed both in lens epithelium and lens fibers. In contrast, gammaF-crystallin is highly expressed in the lens fiber cells. Crystallin gene expression in lens is regulated at the level of transcription by a sparse number of specific DNA-binding transcription factors. Here, we report studies on transcriptional regulation of mouse alphaB- and gammaF-crystallin promoters by specific combinations of Pax6/Pax6(5a), large Mafs (MafA, MafB, c-Maf, and NRL), Sox1, Sox2, Six3, and RARbeta/RXRbeta. Two sets of these factors, co-expressed both in lens epithelium and in lens fibers, were tested in co-transfection assays using cultured lens and non-lens cells. Regulation of alphaB-crystallin was studied in the presence of lens epithelial-factors Pax6, MafB, and RARbeta/RXRbeta, and lens fiber-factors Pax6, MafA, c-Maf, and NRL. Pax6 proteins activated the alphaB-crystallin promoter (-162 to +45) with any combination of Mafs. Addition of RARbeta/RXRbeta further increased its promoter activity. Gel shift assays using lens nuclear extracts demonstrated interactions of Pax6, Maf, and retinoic acid nuclear receptor proteins with two lens-specific regions, the distal LSR1 (-147/-118) and proximal LSR2 (-78/-40), of the alphaB-crystallin promoter. In contrast, Pax6 proteins acted as repressors of gammaF-crystallin promoter activity elicited by a combination of large Mafs, Sox, and RARbeta/RXRbeta proteins in transiently transfected lens and non-lens cells. The results show that Pax6 conversely regulates these two lens crystallin promoters. We propose that the opposite roles of Pax6 in crystallin gene regulation are results of different promoter architectures of the alphaB- and gammaF-crystallin genes, developmentally regulated association of transcription factors with the corresponding cis-regulatory sites, and specific recruitment of transcriptional co-activators and co-repressors by Pax6.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
344
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
351-68
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15522290-Animals, pubmed-meshheading:15522290-CHO Cells, pubmed-meshheading:15522290-Cell Differentiation, pubmed-meshheading:15522290-Cell Line, pubmed-meshheading:15522290-Cells, Cultured, pubmed-meshheading:15522290-Cricetinae, pubmed-meshheading:15522290-Cricetulus, pubmed-meshheading:15522290-Electrophoretic Mobility Shift Assay, pubmed-meshheading:15522290-Epithelial Cells, pubmed-meshheading:15522290-Eye Proteins, pubmed-meshheading:15522290-Genetic Vectors, pubmed-meshheading:15522290-Homeodomain Proteins, pubmed-meshheading:15522290-Humans, pubmed-meshheading:15522290-Lens, Crystalline, pubmed-meshheading:15522290-Mice, pubmed-meshheading:15522290-Paired Box Transcription Factors, pubmed-meshheading:15522290-Plasmids, pubmed-meshheading:15522290-Promoter Regions, Genetic, pubmed-meshheading:15522290-Repressor Proteins, pubmed-meshheading:15522290-Transcription Factors, pubmed-meshheading:15522290-alpha-Crystallins, pubmed-meshheading:15522290-gamma-Crystallins
pubmed:year
2004
pubmed:articleTitle
Transcriptional regulation of mouse alphaB- and gammaF-crystallin genes in lens: opposite promoter-specific interactions between Pax6 and large Maf transcription factors.
pubmed:affiliation
The Department of Ophthalmology, Albert Einstein College of Medicine, 909 Ullmann, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't