Gene Symbol: Kcnq1ot1
Description: KCNQ1 overlapping transcript 1
Alias: Kvlqt1-as, Lit1
Species: mouse

Top Publications

  1. Engemann S, Strödicke M, Paulsen M, Franck O, Reinhardt R, Lane N, et al. Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprinting. Hum Mol Genet. 2000;9:2691-706 pubmed
    ..The conserved region includes the recently identified KCNQ1OT1/Kcnq1ot1 antisense transcripts, flanked by a strikingly conserved cluster of LINE/Line elements and a CpG island ..
  2. Onyango P, Miller W, Lehoczky J, Leung C, Birren B, Wheelan S, et al. Sequence and comparative analysis of the mouse 1-megabase region orthologous to the human 11p15 imprinted domain. Genome Res. 2000;10:1697-710 pubmed
    ..This study provides the first global view of the architecture of an entire imprinted domain and provides candidate sequence elements for subsequent functional analyses. ..
  3. Umlauf D, Goto Y, Cao R, Cerqueira F, Wagschal A, Zhang Y, et al. Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes. Nat Genet. 2004;36:1296-300 pubmed
  4. Fedoriw A, Calabrese J, Mu W, Yee D, Magnuson T. Differentiation-driven nucleolar association of the mouse imprinted Kcnq1 locus. G3 (Bethesda). 2012;2:1521-8 pubmed publisher
    ..allele (1) is stimulated during the differentiation of trophoblast stem cells, (ii) is dependent upon the Kcnq1ot1 noncoding RNA, (3) does not require polycomb repressive complex 2, and (4) is not sufficient to preclude ..
  5. Guseva N, Mondal T, Kanduri C. Antisense noncoding RNA promoter regulates the timing of de novo methylation of an imprinting control region. Dev Biol. 2012;361:403-11 pubmed publisher
    ..Here, we show that a paternal allele of Kcnq1 ICR lacking the Kcnq1ot1 promoter remains unmethylated during spermatogenesis; however, it becomes methylated specifically during pre-..
  6. Redrup L, Branco M, Perdeaux E, Krueger C, Lewis A, Santos F, et al. The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development. 2009;136:525-30 pubmed publisher
    ..The paternally expressed long noncoding RNA (ncRNA) Kcnq1ot1 regulates epigenetic gene silencing in an imprinted gene cluster in cis over a distance of 400 kb in the mouse ..
  7. Korostowski L, Sedlak N, Engel N. The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart. PLoS Genet. 2012;8:e1002956 pubmed publisher
    ..Transcription of the paternally expressed antisense non-coding RNA Kcnq1ot1 silences some neighboring genes in the embryo, while others are unaffected...
  8. Kanduri C. Kcnq1ot1: a chromatin regulatory RNA. Semin Cell Dev Biol. 2011;22:343-50 pubmed publisher
    ..b>Kcnq1ot1 is one such long chromatin-interacting ncRNA that silences multiple genes in the Kcnq1 domain by establishing a ..
  9. Mager J, Montgomery N, de Villena F, Magnuson T. Genome imprinting regulated by the mouse Polycomb group protein Eed. Nat Genet. 2003;33:502-7 pubmed
    ..These data identify Eed as a member of a new class of trans-acting factors that regulate parent-of-origin expression at imprinted loci. ..

More Information


  1. Wagschal A, Sutherland H, Woodfine K, Henckel A, Chebli K, Schulz R, et al. G9a histone methyltransferase contributes to imprinting in the mouse placenta. Mol Cell Biol. 2008;28:1104-13 pubmed
    ..These findings provide the first evidence for the involvement of an HMT and suggest that histone methylation contributes to imprinted gene repression in the trophoblast. ..
  2. Smilinich N, Day C, Fitzpatrick G, Caldwell G, Lossie A, Cooper P, et al. A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. Proc Natl Acad Sci U S A. 1999;96:8064-9 pubmed
    ..We propose that KvDMR1 and/or its associated antisense RNA (KvLQT1-AS) represents an additional imprinting control element or center in the human 11p15.5 and mouse distal 7 imprinted domains. ..
  3. Shin J, Fitzpatrick G, Higgins M. Two distinct mechanisms of silencing by the KvDMR1 imprinting control region. EMBO J. 2008;27:168-78 pubmed
    ..The KvDMR1 ICR contains both the promoter for the Kcnq1ot1 ncRNA and two CTCF-binding sites located within sequences exhibiting repressive activity in enhancer-blocking ..
  4. Salas M, John R, Saxena A, Barton S, Frank D, Fitzpatrick G, et al. Placental growth retardation due to loss of imprinting of Phlda2. Mech Dev. 2004;121:1199-210 pubmed
    ..Consistent with this conclusion, we observed significant placental stunting in BAC-transgenic mice that over-expressed Phlda2 and one flanking gene, Slc22a1l, but did not over-express Cdkn1c. ..
  5. Thakur N, Tiwari V, Thomassin H, Pandey R, Kanduri M, Göndör A, et al. An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region. Mol Cell Biol. 2004;24:7855-62 pubmed
    ..The unmethylated Kcnq1 ICR harbors bidirectional silencer activity and drives expression of an antisense RNA, Kcnq1ot1, which overlaps the Kcnq1 coding region...
  6. Golding M, Magri L, Zhang L, Lalone S, Higgins M, Mann M. Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells. Development. 2011;138:3667-78 pubmed publisher
    ..Here, we investigated the mouse Kcnq1ot1 ncRNA and its role in imprinted gene regulation during preimplantation development by utilizing mouse embryonic ..
  7. Mancini Dinardo D, Steele S, Levorse J, Ingram R, Tilghman S. Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev. 2006;20:1268-82 pubmed
    ..within intron 10 of Kcnq1, contains the promoter for a paternally expressed, noncoding, antisense transcript, Kcnq1ot1. A 244-base-pair deletion of the promoter on the paternal allele leads to the derepression of all silent genes ..
  8. Lewis A, Mitsuya K, Umlauf D, Smith P, Dean W, Walter J, et al. Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation. Nat Genet. 2004;36:1291-5 pubmed
  9. Fitzpatrick G, Soloway P, Higgins M. Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet. 2002;32:426-31 pubmed
    ..These findings support the hypothesis that loss of methylation in BWS patients activates the repressive function of KvDMR1 on the maternal chromosome, resulting in abnormal silencing of CDKN1C and the development of BWS. ..
  10. Mohammad F, Mondal T, Guseva N, Pandey G, Kanduri C. Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development. 2010;137:2493-9 pubmed publisher
    A long noncoding RNA, Kcnq1ot1, regulates the expression of both ubiquitously and tissue-specific imprinted genes within the Kcnq1 domain...
  11. Oh R, Ho R, Mar L, Gertsenstein M, Paderova J, Hsien J, et al. Epigenetic and phenotypic consequences of a truncation disrupting the imprinted domain on distal mouse chromosome 7. Mol Cell Biol. 2008;28:1092-103 pubmed
    ..Thus, all the imprinted genes located in the region and required for normal development are silenced by an IC2-dependent mechanism on the paternal allele...
  12. Cerrato F, Sparago A, Di Matteo I, Zou X, Dean W, Sasaki H, et al. The two-domain hypothesis in Beckwith-Wiedemann syndrome: autonomous imprinting of the telomeric domain of the distal chromosome 7 cluster. Hum Mol Genet. 2005;14:503-11 pubmed
  13. Mancini Dinardo D, Steele S, Ingram R, Tilghman S. A differentially methylated region within the gene Kcnq1 functions as an imprinted promoter and silencer. Hum Mol Genet. 2003;12:283-94 pubmed
    ..We show that the region contains a promoter for a paternally expressed anti-sense transcript, Kcnq1ot1, and we define the extent of the minimal promoter...
  14. Mohammad F, Pandey G, Mondal T, Enroth S, Redrup L, Gyllensten U, et al. Long noncoding RNA-mediated maintenance of DNA methylation and transcriptional gene silencing. Development. 2012;139:2792-803 pubmed publisher
    ..Here, we explored the functional role of the long ncRNA Kcnq1ot1 in the maintenance of transcriptional gene silencing in the one mega-base Kcnq1 imprinted domain in a transgenic ..
  15. Lewis A, Green K, Dawson C, Redrup L, Huynh K, Lee J, et al. Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo. Development. 2006;133:4203-10 pubmed
    ..Repression of these genes is regulated by a non-coding antisense transcript, Kcnq1ot1, which is paternally expressed...
  16. Singh V, Sribenja S, Wilson K, Attwood K, Hillman J, Pathak S, et al. Blocked transcription through KvDMR1 results in absence of methylation and gene silencing resembling Beckwith-Wiedemann syndrome. Development. 2017;144:1820-1830 pubmed publisher
    ..of this mutation resulted in absence of DNA methylation at KvDMR1, which led to biallelic expression of Kcnq1ot1 and suppression of maternally expressed genes...
  17. Asahara S, Etoh H, Inoue H, Teruyama K, Shibutani Y, Ihara Y, et al. Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β-cell mass by epigenetic modification of Cdkn1c. Proc Natl Acad Sci U S A. 2015;112:8332-7 pubmed publisher
    ..The noncoding RNA KCNQ1 overlapping transcript1 (Kcnq1ot1) is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele...
  18. Green K, Lewis A, Dawson C, Dean W, Reinhart B, Chaillet J, et al. A developmental window of opportunity for imprinted gene silencing mediated by DNA methylation and the Kcnq1ot1 noncoding RNA. Mamm Genome. 2007;18:32-42 pubmed
    The Kcnq1 imprinted domain encodes a paternally expressed noncoding RNA Kcnq1ot1 and several paternally repressed protein-coding genes...
  19. Negrón Pérez V, Echevarria F, Huffman S, Rivera R. Determination of allelic expression of h19 in pre- and peri-implantation mouse embryos. Biol Reprod. 2013;88:97 pubmed publisher
    ..In conclusion, loss of imprinting of H19 occurs in the PTGC-containing section of peri-implantation mouse embryos. We speculate that this is part of a physiologic event at the time of implantation in the mouse. ..
  20. Zhao J, Ohsumi T, Kung J, Ogawa Y, Grau D, Sarma K, et al. Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell. 2010;40:939-53 pubmed publisher
    ..Thus, Polycomb proteins interact with a genome-wide family of RNAs, some of which may be used as biomarkers and therapeutic targets for human disease. ..
  21. Pauler F, Barlow D, Hudson Q. Mechanisms of long range silencing by imprinted macro non-coding RNAs. Curr Opin Genet Dev. 2012;22:283-9 pubmed publisher
    ..It is timely, however, to consider alternative explanations consistent with the published data, whereby transcription alone could cause gene silencing at a distance. ..
  22. Saxena A, Carninci P. Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs. Bioessays. 2011;33:830-9 pubmed publisher
    ..Finally, we point to future areas of research and put forward our recommendations for improvements in resources and applications of existing technologies towards targeted outcomes in this active area of research. ..
  23. Lee C, Peng S, Shen L, Lee C, Du T, Kang M, et al. The Role of N-?-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting. Mol Cell. 2017;68:89-103.e7 pubmed publisher
    ..Our study thus links Naa10p mutation-associated Ogden syndrome to defective DNA methylation and genomic imprinting. ..
  24. Hudson Q, Seidl C, Kulinski T, Huang R, Warczok K, Bittner R, et al. Extra-embryonic-specific imprinted expression is restricted to defined lineages in the post-implantation embryo. Dev Biol. 2011;353:420-31 pubmed publisher
    ..These results show that the VYS is an improved model for studying the epigenetic mechanisms regulating extra-embryonic-lineage-specific imprinted expression. ..
  25. Bourc his D, Xu G, Lin C, Bollman B, Bestor T. Dnmt3L and the establishment of maternal genomic imprints. Science. 2001;294:2536-9 pubmed
    ..The key catalytic motifs characteristic of DNA cytosine methyltransferases have been lost from Dnmt3L, and the protein is more likely to act as a regulator of imprint establishment than as a DNA methyltransferase. ..
  26. Bastian H, Gruss P. A murine even-skipped homologue, Evx 1, is expressed during early embryogenesis and neurogenesis in a biphasic manner. EMBO J. 1990;9:1839-52 pubmed
  27. Zhang H, Zeitz M, Wang H, Niu B, Ge S, Li W, et al. Long noncoding RNA-mediated intrachromosomal interactions promote imprinting at the Kcnq1 locus. J Cell Biol. 2014;204:61-75 pubmed publisher
    b>Kcnq1ot1 is a long noncoding ribonucleic acid (RNA; lncRNA) that participates in the regulation of genes within the Kcnq1 imprinting domain...
  28. Jones M, Bogutz A, Lefebvre L. An extended domain of Kcnq1ot1 silencing revealed by an imprinted fluorescent reporter. Mol Cell Biol. 2011;31:2827-37 pubmed publisher
    ..First, we show that Tel7KI is silenced when the noncoding RNA Kcnq1ot1 is biallelically expressed due to absence of maternal DNA methylation at IC2...
  29. Yatsuki H, Watanabe H, Hattori M, Joh K, Soejima H, Komoda H, et al. Sequence-based structural features between Kvlqt1 and Tapa1 on mouse chromosome 7F4/F5 corresponding to the Beckwith-Wiedemann syndrome region on human 11p15.5: long-stretches of unusually well conserved intronic sequences of kvlqt1 between mouse and. DNA Res. 2000;7:195-206 pubmed
    ..Many expressed sequence tags (ESTs) were mapped on this locus. Three genes, Lit1 (Kvlqt1-AS), Mtr1 and Tssc4, were identified and characterized...
  30. Schultz B, Gallicio G, Cesaroni M, Lupey L, Engel N. Enhancers compete with a long non-coding RNA for regulation of the Kcnq1 domain. Nucleic Acids Res. 2015;43:745-59 pubmed publisher
    The imprinted Kcnq1 domain contains a differentially methylated region (KvDMR) in intron 11 of Kcnq1. The Kcnq1ot1 non-coding RNA emerges from the unmethylated paternal KvDMR in antisense direction, resulting in cis-repression of ..
  31. Oh McGinnis R, Bogutz A, Lee K, Higgins M, Lefebvre L. Rescue of placental phenotype in a mechanistic model of Beckwith-Wiedemann syndrome. BMC Dev Biol. 2010;10:50 pubmed publisher
    ..mechanism involving the formation of a repressive nuclear compartment mediated by the long non-coding RNA Kcnq1ot1 initiated from imprinting centre 2 (IC2)...
  32. Kanduri C, Thakur N, Pandey R. The length of the transcript encoded from the Kcnq1ot1 antisense promoter determines the degree of silencing. EMBO J. 2006;25:2096-106 pubmed
    ..Here we show that long transcripts encoded from the Kcnq1ot1 antisense promoter silence the flanking genes more efficiently than short antisense transcripts...
  33. Lefebvre L, Mar L, Bogutz A, Oh McGinnis R, Mandegar M, Paderova J, et al. The interval between Ins2 and Ascl2 is dispensable for imprinting centre function in the murine Beckwith-Wiedemann region. Hum Mol Genet. 2009;18:4255-67 pubmed publisher
    ..Our results show that the deleted interval is not required for normal imprinting on distal Chr 7 and uncover a new imprinted growth phenotype. ..
  34. Higashimoto K, Soejima H, Saito T, Okumura K, Mukai T. Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer. Cytogenet Genome Res. 2006;113:306-12 pubmed
    ..5, which is homologous to mouse chromosome region 7F5, is a well-known imprinted region. The CDKN1C/KCNQ1OT1 imprinted domain, which is one of two imprinted domains at 11p15...
  35. Mahy N, Perry P, Bickmore W. Gene density and transcription influence the localization of chromatin outside of chromosome territories detectable by FISH. J Cell Biol. 2002;159:753-63 pubmed
    ..This is shown to be partly dependent on ongoing transcription. We suggest that local gene density and transcription, rather than the activity of individual genes, influences the organization of chromosomes in the nucleus. ..
  36. Du M, Zhou W, Beatty L, Weksberg R, Sadowski P. The KCNQ1OT1 promoter, a key regulator of genomic imprinting in human chromosome 11p15.5. Genomics. 2004;84:288-300 pubmed
    ..A differentially methylated region in ICR2 regulates the expression of a long transcript called KCNQ1OT1. This paternally expressed transcript negatively regulates several paternally imprinted genes around ICR2...
  37. Jiang Y, Du W, Chu Q, Qin Y, Tuguzbaeva G, Wang H, et al. Downregulation of Long Non-Coding RNA Kcnq1ot1: An Important Mechanism of Arsenic Trioxide-Induced Long QT Syndrome. Cell Physiol Biochem. 2018;45:192-202 pubmed publisher
    ..To evaluate the effect of lncRNA Kcnq1ot1, siRNA and lentivirus-shRNA were synthesized to knockdown lncRNA Kcnq1ot1...