title: A differentially methylated imprinting control region within the Kcnq1 locus harbors a methylation-sensitive chromatin insulator.
abstract: The mechanisms underlying the phenomenon of genomic imprinting remain poorly understood. In one instance, a differentially methylated imprinting control region (ICR) at the H19 locus has been shown to involve a methylation-sensitive chromatin insulator function that apparently partitions the neighboring Igf2 and H19 genes in different expression domains in a parent of origin-dependent manner. It is not known, however, if this mechanism is unique to the Igf2/H19 locus or if insulator function is a common feature in the regulation of imprinted genes. To address this question, we have studied an ICR in the Kcnq1 locus that regulates long range repression on the paternally derived p57Kip2 and Kcnq1 alleles in an imprinting domain that includes Igf2 and H19. We show that this ICR appears to possess a unidirectional chromatin insulator function in somatic cells of both mesodermal and endodermal origins. Moreover, we document that CpG methylation regulates this insulator function suggesting that a methylation-sensitive chromatin insulator is a common theme in the phenomenon of genomic imprinting.
authors.affiliation: Department of Development and Genetics, Evolution Biology Centre, Uppsala University, Norbyvägen 18A, S-752 36 Uppsala, Sweden.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Kanduri
authors.forename: Galina
authors.initials: G
authors.lastname: Fitzpatrick
authors.forename: Rituparna
authors.initials: R
authors.lastname: Mukhopadhyay
authors.forename: Meena
authors.initials: M
authors.lastname: Kanduri
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
authors.forename: Michael
authors.initials: M
authors.lastname: Higgins
authors.forename: Rolf
authors.initials: R
authors.lastname: Ohlsson
mesh_terms: D000483:Alleles; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D003001:Cloning, Molecular; D018899:CpG Islands; D019175:DNA Methylation; D018392:Genomic Imprinting; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D015183:Restriction Mapping; D012260:Ribonucleases / Q000378:metabolism
chemical_list: D002843:Chromatin; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012260:Ribonucleases