CTCF regulates asynchronous replication of the imprinted H19/Igf2 domain.
Asynchronous replication during S phase is a universal characteristic of genomically imprinted genes. Replication timing in imprinted domains is determined epigenetically, as it is parent of origin specific, and is seen in the absence of sequence divergence between the two alleles. At the imprinted H19/Igf2 domain, the methylated paternal allele replicates early while the CTCF-bound maternal allele replicates late during S phase. CTCF regulates the allele-specific epigenetic characteristics of this domain, including methylation, transcription and chromosome conformation. Here we show that maternal, but not paternal inheritance of a mutated H19 imprinting control region, lacking functional CTCF binding sites, underlies a late to early switch in replication timing of the maternal H19/Igf2 domain.
Bergström
Rosita
R
Department of Development and Genetics, Evolutionary Biology Centre, Uppsala University, Uppsala, Sweden.
Whitehead
Joanne
J
Kurukuti
Sreenivasulu
S
Ohlsson
Rolf
R
D000483:Alleles; D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D033481:Chromosomes, Mammalian; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D018392:Genomic Imprinting; D040582:Inheritance Patterns / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D016196:S Phase / Q000235:genetics / Q000502:physiology*
D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; C513121:IGF2 protein, mouse; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D007335:Insulin-Like Growth Factor II