Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2001-6-11
pubmed:databankReference
pubmed:abstractText
We have examined the chromatin structure around and upstream of the transcriptional start site of the human alpha2(I) collagen (COL1A2) gene. Four strong DNase I-hypersensitive sites (HS2-5) were only detected in fibroblasts, and a weaker one (HS1) was identified in type I collagen-negative cells. Another hypersensitive site potentially involved in COL1A2 silencing was found in intron 1 (HS(In)). HS1 and HS2 were mapped within conserved promoter sequences and at locations comparable to the mouse gene. HS3, HS4, and HS5 were likewise mapped approximately 20 kilobases upstream of COL1A2 at about the same position as the mouse far-upstream enhancer and within a remarkably homologous genomic segment. DNase I footprinting identified twelve areas of nuclease protection in the far-upstream region (FU1-12) and within stretches nearly identical to the mouse sequence. The region containing HS3-5 was found to confer high and tissue-specific expression in transgenic mice to the otherwise minimally active COL1A2 promoter. Characterization of the human element documented functional differences with the mouse counterpart. Enhancer activity substantially decreased without the segment containing FU1-7 and HS5, and inclusion of AluI repeats located 3' of HS3 augmented position-independent expression of the transgene. Hence, subtle differences may characterize the regulation of mammalian alpha2(I) collagen genes by evolutionarily conserved sequences.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21754-64
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11279244-Animals, pubmed-meshheading:11279244-Base Sequence, pubmed-meshheading:11279244-Cell Line, pubmed-meshheading:11279244-Chromatin, pubmed-meshheading:11279244-Collagen, pubmed-meshheading:11279244-Collagen Type I, pubmed-meshheading:11279244-Conserved Sequence, pubmed-meshheading:11279244-Crosses, Genetic, pubmed-meshheading:11279244-DNA, pubmed-meshheading:11279244-DNA Footprinting, pubmed-meshheading:11279244-Deoxyribonuclease I, pubmed-meshheading:11279244-Embryonic and Fetal Development, pubmed-meshheading:11279244-Enhancer Elements, Genetic, pubmed-meshheading:11279244-Evolution, Molecular, pubmed-meshheading:11279244-Fibroblasts, pubmed-meshheading:11279244-Gene Expression Regulation, Developmental, pubmed-meshheading:11279244-Humans, pubmed-meshheading:11279244-Lung, pubmed-meshheading:11279244-Mice, pubmed-meshheading:11279244-Mice, Inbred C57BL, pubmed-meshheading:11279244-Mice, Inbred CBA, pubmed-meshheading:11279244-Mice, Transgenic, pubmed-meshheading:11279244-Molecular Sequence Data, pubmed-meshheading:11279244-Promoter Regions, Genetic, pubmed-meshheading:11279244-Restriction Mapping, pubmed-meshheading:11279244-Sequence Alignment, pubmed-meshheading:11279244-Sequence Homology, Nucleic Acid
pubmed:year
2001
pubmed:articleTitle
Characterization of an evolutionarily conserved far-upstream enhancer in the human alpha 2(I) collagen (COL1A2) gene.
pubmed:affiliation
Brookdale Center in the Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine-New York University, New York, New York 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't