Transgenic RNAi reveals essential function for CTCF in H19 gene imprinting.
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). How this 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.
Fedoriw
Andrew M
AM
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stein
Paula
P
Svoboda
Petr
P
Schultz
Richard M
RM
Bartolomei
Marisa S
MS
D000199:Actins / Q000235:genetics; D000818:Animals; D000076246:CCCTC-Binding Factor; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D005260:Female; D005307:Fertilization in Vitro; D018390:Gene Targeting; D018392:Genomic Imprinting; D008098:Litter Size; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics; D009865:Oocytes / Q000378:metabolism*; D034622:RNA Interference; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015053:Zygote / Q000502:physiology
D000199:Actins; D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D012097:Repressor Proteins; C486713:SNURF protein, mouse