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First published online 9 July 2008
doi: 10.1242/dev.024539

Development 135, 2729-2738 (2008)
Published by The Company of Biologists 2008
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Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development

Le-Ben Wan1, Hua Pan2, Sridhar Hannenhalli3, Yong Cheng4, Jun Ma2, Andrew Fedoriw1,*, Victor Lobanenkov5, Keith E. Latham4, Richard M. Schultz2 and Marisa S. Bartolomei1,{dagger}

1 Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
2 Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Department of Genetics and Penn Center for Bioinformatics, University of Pennsylvania, Philadelphia, PA 19104, USA.
4 The Fels Institute for Cancer Research and Molecular Biology, and Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA.
5 Laboratory of Immunopathology, NIAID, NIH, Rockville, MD 20852, USA.

{dagger} Author for correspondence (e-mail: bartolom{at}mail.med.upenn.edu)

Accepted 15 June 2008

CTCF is a multifunctional nuclear factor involved in epigenetic regulation. Despite recent advances that include the systematic discovery of CTCF-binding sites throughout the mammalian genome, the in vivo roles of CTCF in adult tissues and during embryonic development are largely unknown. Using transgenic RNAi, we depleted maternal stores of CTCF from growing mouse oocytes, and identified hundreds of misregulated genes. Moreover, our analysis suggests that CTCF predominantly activates or derepresses transcription in oocytes. CTCF depletion causes meiotic defects in the egg, and mitotic defects in the embryo that are accompanied by defects in zygotic gene expression, and culminate in apoptosis. Maternal pronuclear transfer and CTCF mRNA microinjection experiments indicate that CTCF is a mammalian maternal effect gene, and that persistent transcriptional defects rather than persistent chromosomal defects perturb early embryonic development. This is the first study detailing a global and essential role for CTCF in mouse oocytes and preimplantation embryos.

Key words: CTCF, Mouse, Oocyte, Preimplantation embryo, Meiosis


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