CTCF Elements Direct Allele-Specific Undermethylation at the Imprinted H19 Locus

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CTCF Elements Direct Allele-Specific Undermethylation at the Imprinted H19 Locus

The H19 imprinted gene locus is regulated by an upstream 2 kb imprinting control region (ICR) that influences allele-specific expression, DNA methylation, and replication timing. This ICR becomes de novo methylated during late spermatogenesis in the male but emerges from oogenesis in an unmethylated form, and this allele-specific pattern is then maintained throughout early development and in al...

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CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locus.

Imprinting at the H19/Igf2 locus depends on a differentially methylated domain (DMD) acting as a maternal-specific, methylation-sensitive insulator and a paternal-specific locus of hypermethylation. Four repeats in the DMD bind CTCF on the maternal allele and have been proposed to recruit methylation on the paternal allele. We deleted the four repeats and assayed the effects of the mutation at ...

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CTCF is the master organizer of domain-wide allele-specific chromatin at the H19/Igf2 imprinted region.

A paternally methylated imprinting control region (ICR) directs allele-specific expression of the imprinted H19 and Igf2 genes. CTCF protein binding in the ICR is required in the maternal chromosome for insulating Igf2 from the shared enhancers, initiation of the H19 promoter transcription, maintaining DNA hypomethylation, and chromosome loop formation. Using novel quantitative allele-specific ...

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A transcriptional insulator at the imprinted H19/Igf2 locus.

Igf2 and H19 exhibit parent-of-origin-specific monoallelic expression. H19 is expressed from the maternal chromosome and Igf2 from the paternal. The two genes share enhancer elements and monoallelic expression of both genes is dependent on cis-acting sequences upstream of the H19 promoter. In this work we examine the mechanisms by which this region silences the maternal Igf2 allele and we demon...

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More than insulator: multiple roles of CTCF at the H19-Igf2 imprinted domain

CTCF (CCCTC-binding factor)-mediated insulation at the H19-Insulin-like growth factor 2 (Igf2) imprinted domain is a classic example for imprinted gene regulation. DNA methylation difference in the imprinting control region (ICR) is inherited from the gametes and subsequently determines parental allele-specific enhancer blocking and imprinted expression in the soma. Recent genetic studies showe...

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ژورنال

عنوان ژورنال: Current Biology

سال: 2004

ISSN: 0960-9822

DOI: 10.1016/j.cub.2004.05.041