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Vol. 17, No. 5, pp. 586-590, March 1, 2003
1 Department of Development & Genetics, Evolution Biology
Centre, Uppsala University, S-752 36 Uppsala, Sweden;
2 Laboratory of Immunopathology, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Bethesda,
Maryland 20892-0760, USA; 3 Ludwig Institute for Cancer
Research, Biomedical Center, S-751 24 Uppsala, Sweden
The repression of the maternally inherited Igf2 allele has
been proposed to depend on a methylation-sensitive chromatin insulator organized by the 11 zinc finger protein CTCF at the H19
imprinting control region (ICR). Here we document that point mutations
of the nucleotides in physical contact with CTCF within the endogenous H19 ICR lead to loss of CTCF binding and Igf2
imprinting only when passaged through the female
germline. This effect is accompanied by a significant loss of
methylation protection of the maternally derived H19 ICR.
Because CTCF interacts with other imprinting control regions, it
emerges as a central factor responsible for interpreting and
propagating gamete-derived epigenetic marks and for organizing
epigenetically controlled expression domains.
[Keywords: Genomic imprinting; Igf2; chromatin insulator; CTCF; DNA methylation]
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