CTCF elements direct allele-specific undermethylation at the imprinted H19 locus

Eyal Rand, Ittai Ben-Porath, Ilana Keshet, Howard Cedar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The H19 imprinted gene locus is regulated by an upstream 2 kb imprinting control region (ICR) that influences allele-specific expression, DNA methylation [1], and replication timing [2]. This ICR becomes de novo methylated during late spermatogenesis in the male [3] but emerges from oogenesis in an unmethylated form, and this allele-specific pattern is then maintained throughout early development [4] and in all tissues of the mouse [5]. We have used a genetic approach involving transfection into embryonic stem (ES) cells in order to decipher how the maternal allele is protected from de novo methylation at the time of implantation [6]. Our studies show that CCCTC binding factor (CTCF) boundary elements within the ICR [7, 8] have the ability to prevent de novo methylation on the maternal allele. Since CTCF does not recognize its binding sequence when methylated [9, 10], this reaction does not occur on the paternal allele, thus preserving the gamete-derived, allele-specific pattern. These results suggest that CTCF may play a general role in the maintenance of differential methylation patterns in vivo.

Original languageAmerican English
Pages (from-to)1007-1012
Number of pages6
JournalCurrent Biology
Volume14
Issue number11
DOIs
StatePublished - 8 Jun 2004

Bibliographical note

Funding Information:
This research was supported by grants from the National Institutes of Health, the Israel Cancer Research Foundation, and the Belfer Foundation.

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