KCNQ1OT1

KCNQ1 overlapping transcript 1, also known as KCNQ1OT1, is a long non-coding RNA gene found in the KCNQ1 locus. This locus consists of 8–10 protein-coding genes, specifically expressed from the maternal allele (including the KCNQ1 gene), and the paternally expressed non-coding RNA gene KCNQ1OT1.[2] KCNQ1OT1 and KCNQ1 are imprinted genes and are part of an imprinting control region (ICR). Mitsuya identified that KCNQ1OT1 is an antisense transcript of KCNQ1. KCNQ1OT1 is a paternally expressed allele and KCNQ1 is a maternally expressed allele.[3] KCNQ1OT1 is a nuclear, 91 kb transcript, found in close proximity to the nucleolus in certain cell types.[4][5]

KCNQ1OT1
Identifiers
AliasesKCNQ1OT1, KCNQ1-AS2, KCNQ10T1, KvDMR1, KvLQT1-AS, LIT1, NCRNA00012, Kncq1, KCNQ1 opposite strand/antisense transcript 1 (non-protein coding), KCNQ1 opposite strand/antisense transcript 1
External IDsOMIM: 604115 GeneCards: KCNQ1OT1
Orthologs
SpeciesHumanMouse
Entrez

10984

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed search[1]n/a
Wikidata
View/Edit Human

It interacts with chromatin, the histone methyltransferase G9a (responsible for the mono- and dimethylation of histone 3 lysine 9, H3K9), and the Polycomb Repressive Complex 2, PRC2, (responsible for the trimethylation of H3K27).[4] It plays an important role in the transcriptional silencing of the KCNQ1 locus by regulating histone methylation.[2] An 890 bp region at the 5′ end of KCNQ1OT1 acts as a silencing domain.[6][7] This region regulates CpG methylation levels of somatically acquired differentially methylated regions (DMRs), mediates the interaction of KCNQ1OT1 with chromatin and with DNA (cytosine-5)-methyltransferase 1 (DNMT1), but does not affect the interactions of histone methyltransferases with KCNQ1OT1.[7]

The misregulation of the imprinted gene KCNQ1OT1 can lead to a variety of abnormalities. The loss of the maternal methylation of the KCNQ1OT1 allele is most commonly associated with Beckwith-Wiedemann syndrome.[8] The deletion of KCNQ1OT1 in males can result in a removal of the repressor in six cis genes.[9] Offspring from the males that had KCNQ1OT1 knocked out weighed 20–25% less than the control.[9] If the deletion occurred in females, their offspring had no growth restrictions. Furthermore, uniparental paternal disomy (UPD) of KCNQ1OT1 is strongly associated with Wilms’ tumor. In fact, three out of four patients with Beckwith-Wiedemann Syndrome and Wilms’ tumor had UPD.[10] When KCNQ1OT1 transcript is truncated, normally repressed alleles on the paternal chromosome are instead expressed.[11] As the evidence shows, the misregulation of KCNQ1OT1 can lead to disastrous physical and genetic effects.

See also
  • Long noncoding RNA
  • Beckwith-Wiedemann syndrome

References
  1. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  2. Kanduri C (June 2011). "Kcnq1ot1: a chromatin regulatory RNA". Seminars in Cell & Developmental Biology. 22 (4): 343–350. doi:10.1016/j.semcdb.2011.02.020. PMID 21345374.
  3. Mitsuya K, Meguro M, Lee MP, Katoh M, Schulz TC, Kugoh H, Yoshida MA, Niikawa N, Feinberg AP, Oshimura M (July 1999). "LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids". Human Molecular Genetics. 8 (7): 1209–1217. doi:10.1093/hmg/8.7.1209. PMID 10369866.
  4. Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C (October 2008). "Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation". Molecular Cell. 32 (2): 232–246. doi:10.1016/j.molcel.2008.08.022. PMID 18951091.
  5. Fedoriw AM, Calabrese JM, Mu W, Yee D, Magnuson T (December 2012). "Differentiation-driven nucleolar association of the mouse imprinted Kcnq1 locus". G3. 2 (12): 1521–1528. doi:10.1534/g3.112.004226. PMC 3516474. PMID 23275875.
  6. Mohammad F, Pandey RR, Nagano T, Chakalova L, Mondal T, Fraser P, Kanduri C (June 2008). "Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region". Molecular and Cellular Biology. 28 (11): 3713–3728. doi:10.1128/MCB.02263-07. PMC 2423283. PMID 18299392.
  7. Mohammad F, Mondal T, Guseva N, Pandey GK, Kanduri C (August 2010). "Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1". Development. 137 (15): 2493–2499. doi:10.1242/dev.048181. PMID 20573698.
  8. Engel JR, Smallwood A, Harper A, Higgins MJ, Oshimura M, Reik W, Schofield PN, Maher ER (December 2000). "Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome". Journal of Medical Genetics. 37 (12): 921–926. doi:10.1136/jmg.37.12.921. PMC 1734494. PMID 11106355.
  9. Fitzpatrick GV, Soloway PD, Higgins MJ (November 2002). "Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1". Nature Genetics. 32 (3): 426–431. doi:10.1038/ng988. PMID 12410230.
  10. Henry I, Bonaiti-Pellié C, Chehensse V, Beldjord C, Schwartz C, Utermann G, Junien C (June 1991). "Uniparental paternal disomy in a genetic cancer-predisposing syndrome". Nature. 351 (6328): 665–667. doi:10.1038/351665a0. PMID 1675767.
  11. Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM (May 2006). "Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes". Genes & Development. 20 (10): 1268–1282. doi:10.1101/gad.1416906. PMC 1472902. PMID 16702402.

Further reading
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