title: CTCF-binding sites within the H19 ICR differentially regulate local chromatin structures and cis-acting functions.
abstract: It is generally assumed that CTCF-binding sites are synonymous with the demarcation of expression domains by promoting the formation of chromatin loops. We have proposed earlier, however, that such features may be context-dependent. In support of this notion, we show here that chromatin loop structures, impinging on CTCF-binding sites 1/2 and 3/4 at the 5' and 3'-ends, respectively, within the maternal allele of the H19 imprinting control region (ICR), differ significantly. Although abrogation of CTCF binding to the maternal H19 ICR allele results in loss of chromatin loops in the 3'-region, there is a dramatic gain of long-range chromatin loops impinging on the 5'-region. As the degree of occupancy of its four CTCF-binding sites discriminates between the chromatin insulator and replication timing functions, we submit that the CTCF-binding sites within the H19 ICR are functionally diverse and organize context-dependent higher order chromatin conformations.
authors.affiliation: Department of Development and Genetics, Evolution Biology Centre, Uppsala University, Uppsala, Sweden. sguibert@unistra.fr
authors.forename: Sylvain
authors.initials: S
authors.lastname: Guibert
authors.forename: Zhihu
authors.initials: Z
authors.lastname: Zhao
authors.forename: Mikael
authors.initials: M
authors.lastname: Sjölinder
authors.forename: Anita
authors.initials: A
authors.lastname: Göndör
authors.forename: Alejandro
authors.initials: A
authors.lastname: Fernandez
authors.forename: Vinod
authors.initials: V
authors.lastname: Pant
authors.forename: Rolf
authors.initials: R
authors.lastname: Ohlsson
mesh_terms: D000483:Alleles; D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D003433:Crosses, Genetic; D019175:DNA Methylation; D004261:DNA Replication; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D025941:Protein Interaction Mapping; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors; D015533:Transcriptional Activation
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; 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