Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2000-9-18
pubmed:abstractText
In mammals, a subset of genes inherit gametic marks that establish parent of origin-dependent expression patterns in the soma ([1] and references therein). The currently most extensively studied examples of this phenomenon, termed genomic imprinting, are the physically linked Igf2 (insulin-like growth factor II) and H19 genes, which are expressed mono-allelically from opposite parental alleles [1] [2]. The repressed status of the maternal Igf2 allele is due to cis elements that prevent the H19 enhancers [3] from accessing the Igf2 promoters on the maternal chromosome [4] [5]. A differentially methylated domain (DMD) in the 5' flank of H19 is maintained paternally methylated and maternally unmethylated [6] [7]. We show here by gel-shift and chromatin immunopurification analyses that binding of the highly conserved multivalent factor CTCF ([8] [9] and references therein) to the H19 DMD is methylation-sensitive and parent of origin-dependent. Selectively mutating CTCF-contacting nucleotides, which were identified by methylation interference within the extended binding sites initially revealed by nuclease footprinting, abrogated the H19 DMD enhancer-blocking property. These observations suggest that molecular mechanisms of genomic imprinting may use an unusual ability of CTCF to interact with a diverse spectrum of variant target sites, some of which include CpGs that are responsible for methylation-sensitive CTCF binding in vitro and in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0960-9822
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
853-6
pubmed:dateRevised
2011-10-7
pubmed:meshHeading
pubmed-meshheading:10899010-Animals, pubmed-meshheading:10899010-Base Sequence, pubmed-meshheading:10899010-Binding Sites, pubmed-meshheading:10899010-DNA, pubmed-meshheading:10899010-DNA Methylation, pubmed-meshheading:10899010-DNA-Binding Proteins, pubmed-meshheading:10899010-Enhancer Elements, Genetic, pubmed-meshheading:10899010-Female, pubmed-meshheading:10899010-Insulin-Like Growth Factor II, pubmed-meshheading:10899010-Male, pubmed-meshheading:10899010-Mice, pubmed-meshheading:10899010-Molecular Sequence Data, pubmed-meshheading:10899010-Muscle Proteins, pubmed-meshheading:10899010-Protein Binding, pubmed-meshheading:10899010-RNA, Untranslated, pubmed-meshheading:10899010-Repressor Proteins, pubmed-meshheading:10899010-Transcription Factors, pubmed-meshheading:10899010-Zinc Fingers
pubmed:year
2000
pubmed:articleTitle
Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive.
pubmed:affiliation
Department of Development and Genetics, Uppsala University, Uppsala, S-75236, Sweden.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't