Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development.
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.
Wan
Le-Ben
LB
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Pan
Hua
H
Hannenhalli
Sridhar
S
Cheng
Yong
Y
Ma
Jun
J
Fedoriw
Andrew
A
Lobanenkov
Victor
V
Latham
Keith E
KE
Schultz
Richard M
RM
Bartolomei
Marisa S
MS
D000818:Animals; D017209:Apoptosis; D000076246:CCCTC-Binding Factor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D008540:Meiosis; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis; D009865:Oocytes / Q000502:physiology*; D009866:Oogenesis; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*
D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D012097:Repressor Proteins