Source:http://linkedlifedata.com/resource/pubmed/id/10899010
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
2000-9-18
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCCTC-binding factor,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/H19 long non-coding RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Untranslated,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0960-9822
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
853-6
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pubmed:dateRevised |
2011-10-7
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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
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pubmed:year |
2000
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pubmed:articleTitle |
Functional association of CTCF with the insulator upstream of the H19 gene is parent of origin-specific and methylation-sensitive.
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pubmed:affiliation |
Department of Development and Genetics, Uppsala University, Uppsala, S-75236, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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