title: Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus.
abstract: Kcnq1ot1 is a long noncoding ribonucleic acid (RNA; lncRNA) that participates in the regulation of genes within the Kcnq1 imprinting domain. Using a novel RNA-guided chromatin conformation capture method, we demonstrate that the 5' region of Kcnq1ot1 RNA orchestrates a long-range intrachromosomal loop between KvDMR1 and the Kcnq1 promoter that is required for maintenance of imprinting. PRC2 (polycomb repressive complex 2), which participates in the allelic repression of Kcnq1, is also recruited by Kcnq1ot1 RNA via EZH2. Targeted suppression of Kcnq1ot1 lncRNA prevents the creation of this long-range intrachromosomal loop and causes loss of Kcnq1 imprinting. These observations delineate a novel mechanism by which an lncRNA directly builds an intrachromosomal interaction complex to establish allele-specific transcriptional gene silencing over a large chromosomal domain.
authors.affiliation: Stem Cell and Cancer Center, First Affiliated Hospital, Jilin University, Changchun 130061, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zeitz
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Beibei
authors.initials: B
authors.lastname: Niu
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
authors.forename: Guanjun
authors.initials: G
authors.lastname: Wang
authors.forename: Guanxiang
authors.initials: G
authors.lastname: Qian
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Higgins
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
mesh_terms: D000483:Alleles; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D018392:Genomic Imprinting / Q000235:genetics; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C493965:Cdkn1c protein, mouse; D002843:Chromatin; D050761:Cyclin-Dependent Kinase Inhibitor p57; D051657:KCNQ1 Potassium Channel; C449939:KCNQ1OT1 RNA; C496910:Kcnq1 protein, mouse; D062085:RNA, Long Noncoding; D004247:DNA; D063151:Polycomb Repressive Complex 2