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Science 9 January 2004:
Vol. 303. no. 5655, pp. 238 - 240
DOI: 10.1126/science.1090934
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Reports

Transgenic RNAi Reveals Essential Function for CTCF in H19 Gene Imprinting

Andrew M. Fedoriw,1,2 Paula Stein,3 Petr Svoboda,3 Richard M. Schultz,3 Marisa S. Bartolomei1,2*

The imprinted regulation of H19 and Insulin-like growth factor 2 expression involves binding of the vertebrate insulator protein, CCCTC binding factor (CTCF), to the maternally hypomethylated differentially methylated domain (DMD). Howthis hypomethylated state is maintained during oogenesis and the role of CTCF, if any, in this process are not understood. With the use of a transgenic RNA interference (RNAi)–based approach to generate oocytes with reduced amounts of CTCF protein, we found increased methylation of the H19 DMD and decreased developmental competence of CTCF-deficient oocytes. Our results suggest that CTCF protects the H19 DMD from de novo methylation during oocyte growth and is required for normal preimplantation development.

1 Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

* To whom correspondence should be addressed. E-mail: bartolom{at}mail.med.upenn.edu

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