Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-20
pubmed:abstractText
Comparative analysis of the human and mouse genomic sequences downstream of the apolipoprotein E gene (APOE) revealed a highly conserved element with previously undefined function. In reporter gene transfection studies, this element which is located approximately 42 kb distal to APOE was found to have silencer activity in a subset of cell lines examined. Analysis of transgenic mice containing a fusion construct linking this distal 631 bp conserved element to a reporter gene comprised of the human APOE gene with its proximal promoter resulted in robust brain expression of the transgenic human apoE mRNA in three independent transgenic lines, supporting the identification of a novel brain controlling region (BCR). Further studies using immunohistochemistry revealed widespread human apoE localization throughout the brains of the BCR-apoE transgenic mice with prominent expression in the cortex and diencephalon. In addition, double-label immunofluorescence performed on brain sections and cultures of primary cortical cells localized human apoE protein to cortical neurons and microglia. These studies demonstrate that comparative sequence analysis is a successful strategy to predict candidate regulatory regions in vivo, although they do not imply that this element controls apoE expression physiologically.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
1676
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-50
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14732489-Animals, pubmed-meshheading:14732489-Apolipoproteins E, pubmed-meshheading:14732489-Base Sequence, pubmed-meshheading:14732489-Blotting, Western, pubmed-meshheading:14732489-Cells, Cultured, pubmed-meshheading:14732489-Cerebral Cortex, pubmed-meshheading:14732489-Chromosome Mapping, pubmed-meshheading:14732489-DNA Primers, pubmed-meshheading:14732489-Databases, Nucleic Acid, pubmed-meshheading:14732489-Enhancer Elements, Genetic, pubmed-meshheading:14732489-Fluorescent Antibody Technique, pubmed-meshheading:14732489-Gene Expression, pubmed-meshheading:14732489-Genes, Reporter, pubmed-meshheading:14732489-Genomics, pubmed-meshheading:14732489-Humans, pubmed-meshheading:14732489-Immunohistochemistry, pubmed-meshheading:14732489-In Situ Hybridization, pubmed-meshheading:14732489-Mice, pubmed-meshheading:14732489-Mice, Transgenic, pubmed-meshheading:14732489-Molecular Sequence Data, pubmed-meshheading:14732489-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:14732489-Sequence Alignment, pubmed-meshheading:14732489-Transfection
pubmed:year
2004
pubmed:articleTitle
Identification of a novel enhancer of brain expression near the apoE gene cluster by comparative genomics.
pubmed:affiliation
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't