Multiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 imprinting control region.
The 5' region of the H19 gene harbors a methylation-sensitive chromatin insulator within an imprinting control region (ICR). Insertional mutagenesis in combination with episomal assays identified nucleosome positioning sequences (NPSs) that set the stage for the remarkably precise distribution of the four target sites for the chromatin insulator protein CTCF to nucleosome linker sequences in the H19 ICR. Changing positions of the NPSs resulted in loss of both CTCF target site occupancy and insulator function, suggesting that the NPSs optimize the fidelity of the insulator function. We propose that the NPSs ensure the fidelity of the repressed status of the maternal Igf2 allele during development by constitutively maintaining availability of the CTCF target sites.
Kanduri
Meena
M
Department of Development & Genetics, Evolution Biology Centre, Uppsala University, S-752 36 Uppsala, Sweden.
Kanduri
Chandrasekhar
C
Mariano
Piero
P
Vostrov
Alexander A
AA
Quitschke
Wolfgang
W
Lobanenkov
Victor
V
Ohlsson
Rolf
R
D000818:Animals; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D019901:Locus Control Region / Q000235:genetics*; D051379:Mice; D016254:Mutagenesis, Insertional; D009707:Nucleosomes / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; D009707:Nucleosomes; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors