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'''KCNQ1 overlapping transcript 1''', also known as '''KCNQ1OT1''', is a [[long non-coding RNA]] [[gene]] found in the KCNQ1 [[Locus (genetics)|locus]]. This locus consists of 8-10 protein-coding genes, [[Genomic imprinting|specifically expressed from the maternal allele]] (including the [[KCNQ1]] gene), and the paternally expressed non-coding RNA gene KCNQ1OT1.<ref name="pmid21345374">{{cite journal | vauthors = Kanduri C | title = Kcnq1ot1: a chromatin regulatory RNA | journal = Seminars in Cell & Developmental Biology | volume = 22 | issue = 4 | pages = 343–50 | date = June 2011 | pmid = 21345374 | doi = 10.1016/j.semcdb.2011.02.020 }}</ref>  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.<ref>{{cite journal | vauthors = Mitsuya K, Meguro M, Lee MP, Katoh M, Schulz TC, Kugoh H, Yoshida MA, Niikawa N, Feinberg AP, Oshimura M | title = LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids | journal = Human Molecular Genetics | volume = 8 | issue = 7 | pages = 1209–17 | date = July 1999 | pmid = 10369866 | doi=10.1093/hmg/8.7.1209}}</ref> KCNQ1OT1 is a nuclear, 91 kb transcript, found in close proximity to the [[nucleolus]] in certain cell types.<ref name="pmid18951091">{{cite journal | vauthors = Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J, Nagano T, Mancini-Dinardo D, Kanduri C | title = Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation | journal = Molecular Cell | volume = 32 | issue = 2 | pages = 232–46 | date = October 2008 | pmid = 18951091 | doi = 10.1016/j.molcel.2008.08.022 }}</ref><ref name="pmid23275875">{{cite journal | vauthors = Fedoriw AM, Calabrese JM, Mu W, Yee D, Magnuson T | title = Differentiation-driven nucleolar association of the mouse imprinted Kcnq1 locus | journal = G3 | volume = 2 | issue = 12 | pages = 1521–8 | date = December 2012 | pmid = 23275875 | doi = 10.1534/g3.112.004226 | pmc=3516474}}</ref>
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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).<ref name="pmid18951091" /> It plays an important role in the [[transcriptional silencing]] of the KCNQ1 locus by regulating histone methylation.<ref name="pmid21345374" /> An 890 [[base pair|bp]] region at the [[Directionality (molecular biology)|5']] end of KCNQ1OT1 acts as a silencing domain.<ref name="pmid18299392">{{cite journal | vauthors = Mohammad F, Pandey RR, Nagano T, Chakalova L, Mondal T, Fraser P, Kanduri C | title = Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region | journal = Molecular and Cellular Biology | volume = 28 | issue = 11 | pages = 3713–28 | date = June 2008 | pmid = 18299392 | pmc = 2423283 | doi = 10.1128/MCB.02263-07 }}</ref><ref name="pmid20573698">{{cite journal | vauthors = Mohammad F, Mondal T, Guseva N, Pandey GK, Kanduri C | title = Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1 | journal = Development | volume = 137 | issue = 15 | pages = 2493–9 | date = August 2010 | pmid = 20573698 | doi = 10.1242/dev.048181 }}</ref> This region regulates [[DNA methylation|CpG methylation]] levels of [[Somatic (biology)|somatic]]ally 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.<ref name="pmid20573698" />
{{GNF_Protein_box
| image =
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| PDB =
| Name = KCNQ1 overlapping transcript 1
| HGNCid = 6295
| Symbol = KCNQ1OT1
| AltSymbols =; KCNQ10T1; KvDMR1; KvLQT1-AS; LIT1
| OMIM = 604115
| ECnumber =
| Homologene =
| MGIid =
| Function =
| Component =
| Process =
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'''KCNQ1 overlapping transcript 1''', also known as '''KCNQ1OT1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: KCNQ1OT1 KCNQ1 overlapping transcript 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10984| accessdate = }}</ref>


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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|Beckwith-Wiedemann syndrome]].<ref>{{cite journal | vauthors = Engel JR, Smallwood A, Harper A, Higgins MJ, Oshimura M, Reik W, Schofield PN, Maher ER | title = Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome | journal = Journal of Medical Genetics | volume = 37 | issue = 12 | pages = 921–6 | date = December 2000 | pmid = 11106355 | pmc = 1734494 | doi=10.1136/jmg.37.12.921}}</ref> The deletion of KCNQ1OT1 in males can result in a removal of the repressor in six cis genes.<ref name=":0">{{cite journal | vauthors = Fitzpatrick GV, Soloway PD, Higgins MJ | title = Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1 | journal = Nature Genetics | volume = 32 | issue = 3 | pages = 426–31 | date = November 2002 | pmid = 12410230 | doi = 10.1038/ng988 }}</ref> Offspring from the males that had KCNQ1OT1 knocked out  weighed 20-25% less than the control.<ref name=":0" />  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|Wilms’ tumor.]]  In fact, three out of four patients with Beckwith-Wiedemann Syndrome and Wilms’ tumor had UPD.<ref>{{cite journal | vauthors = Henry I, Bonaiti-Pellié C, Chehensse V, Beldjord C, Schwartz C, Utermann G, Junien C | title = Uniparental paternal disomy in a genetic cancer-predisposing syndrome | language = en | journal = Nature | volume = 351 | issue = 6328 | pages = 665–7 | date = June 1991 | pmid = 1675767 | doi = 10.1038/351665a0 }}</ref> When KCNQ1OT1 transcript is truncated, normally repressed alleles on the paternal chromosome are instead expressed.<ref>{{cite journal | vauthors = Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM | title = Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes | language = en | journal = Genes & Development | volume = 20 | issue = 10 | pages = 1268–82 | date = May 2006 | pmid = 16702402 | pmc = 1472902 | doi = 10.1101/gad.1416906 }}</ref> As the evidence shows, the misregulation of KCNQ1OT1 can lead to disastrous physical and genetic effects.
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==References==
== See also ==
{{reflist|2}}
* [[Long noncoding RNA]]
==Further reading==
* [[Beckwith-Wiedemann syndrome]]
{{refbegin | 2}}
 
{{PBB_Further_reading
== References ==
| citations =
{{reflist|33em}}
*{{cite journal | author=Adams MD, Kerlavage AR, Fleischmann RD, ''et al.'' |title=Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. |journal=Nature |volume=377 |issue= 6547 Suppl |pages= 3-174 |year= 1995 |pmid= 7566098 |doi= }}
 
*{{cite journal | author=Hillier LD, Lennon G, Becker M, ''et al.'' |title=Generation and analysis of 280,000 human expressed sequence tags. |journal=Genome Res. |volume=6 |issue= 9 |pages= 807-28 |year= 1997 |pmid= 8889549 |doi= }}
== Further reading ==
*{{cite journal | author=Lee MP, DeBaun MR, Mitsuya K, ''et al.'' |title=Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 9 |pages= 5203-8 |year= 1999 |pmid= 10220444 |doi= }}
{{refbegin|33em}}
*{{cite journal | author=Mitsuya K, Meguro M, Lee MP, ''et al.'' |title=LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids. |journal=Hum. Mol. Genet. |volume=8 |issue= 7 |pages= 1209-17 |year= 1999 |pmid= 10369866 |doi= }}
* {{cite journal | vauthors = Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O | title = Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence | journal = Nature | volume = 377 | issue = 6547 Suppl | pages = 3–174 | date = September 1995 | pmid = 7566098 | doi = <!-- none available --> | url = http://www.columbia.edu/itc/biology/pollack/w4065/client_edit/readings/nature377_3.pdf | format = PDF }}
*{{cite journal | author=Smilinich NJ, Day CD, Fitzpatrick GV, ''et al.'' |title=A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 14 |pages= 8064-9 |year= 1999 |pmid= 10393948 |doi= }}
* {{cite journal | vauthors = Lee MP, DeBaun MR, Mitsuya K, Galonek HL, Brandenburg S, Oshimura M, Feinberg AP | title = Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 9 | pages = 5203–8 | date = April 1999 | pmid = 10220444 | pmc = 21842 | doi = 10.1073/pnas.96.9.5203 }}
*{{cite journal | author=DeBaun MR, Niemitz EL, McNeil DE, ''et al.'' |title=Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. |journal=Am. J. Hum. Genet. |volume=70 |issue= 3 |pages= 604-11 |year= 2002 |pmid= 11813134 |doi= }}
* {{cite journal | vauthors = Mitsuya K, Meguro M, Lee MP, Katoh M, Schulz TC, Kugoh H, Yoshida MA, Niikawa N, Feinberg AP, Oshimura M | title = LIT1, an imprinted antisense RNA in the human KvLQT1 locus identified by screening for differentially expressed transcripts using monochromosomal hybrids | journal = Human Molecular Genetics | volume = 8 | issue = 7 | pages = 1209–17 | date = July 1999 | pmid = 10369866 | doi = 10.1093/hmg/8.7.1209 }}
*{{cite journal | author=Cerrato F, Vernucci M, Pedone PV, ''et al.'' |title=The 5' end of the KCNQ1OT1 gene is hypomethylated in the Beckwith-Wiedemann syndrome. |journal=Hum. Genet. |volume=111 |issue= 1 |pages= 105-7 |year= 2002 |pmid= 12136243 |doi= 10.1007/s00439-002-0751-1 }}
* {{cite journal | vauthors = Smilinich NJ, Day CD, Fitzpatrick GV, Caldwell GM, Lossie AC, Cooper PR, Smallwood AC, Joyce JA, Schofield PN, Reik W, Nicholls RD, Weksberg R, Driscoll DJ, Maher ER, Shows TB, Higgins MJ | title = A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 14 | pages = 8064–9 | date = July 1999 | pmid = 10393948 | pmc = 22188 | doi = 10.1073/pnas.96.14.8064 }}
*{{cite journal | author=DeBaun MR, Niemitz EL, Feinberg AP |title=Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. |journal=Am. J. Hum. Genet. |volume=72 |issue= 1 |pages= 156-60 |year= 2003 |pmid= 12439823 |doi= }}
* {{cite journal | vauthors = DeBaun MR, Niemitz EL, McNeil DE, Brandenburg SA, Lee MP, Feinberg AP | title = Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects | journal = American Journal of Human Genetics | volume = 70 | issue = 3 | pages = 604–11 | date = March 2002 | pmid = 11813134 | pmc = 384940 | doi = 10.1086/338934 }}
*{{cite journal | author=Gicquel C, Gaston V, Mandelbaum J, ''et al.'' |title=In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. |journal=Am. J. Hum. Genet. |volume=72 |issue= 5 |pages= 1338-41 |year= 2003 |pmid= 12772698 |doi= }}
* {{cite journal | vauthors = Cerrato F, Vernucci M, Pedone PV, Chiariotti L, Sebastio G, Bruni CB, Riccio A | title = The 5' end of the KCNQ1OT1 gene is hypomethylated in the Beckwith-Wiedemann syndrome | journal = Human Genetics | volume = 111 | issue = 1 | pages = 105–7 | date = July 2002 | pmid = 12136243 | doi = 10.1007/s00439-002-0751-1 }}
*{{cite journal | author=Diaz-Meyer N, Day CD, Khatod K, ''et al.'' |title=Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. |journal=J. Med. Genet. |volume=40 |issue= 11 |pages= 797-801 |year= 2004 |pmid= 14627666 |doi= }}
* {{cite journal | vauthors = DeBaun MR, Niemitz EL, Feinberg AP | title = Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19 | journal = American Journal of Human Genetics | volume = 72 | issue = 1 | pages = 156–60 | date = January 2003 | pmid = 12439823 | pmc = 378620 | doi = 10.1086/346031 }}
*{{cite journal | author=Soejima H, Nakagawachi T, Zhao W, ''et al.'' |title=Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer. |journal=Oncogene |volume=23 |issue= 25 |pages= 4380-8 |year= 2004 |pmid= 15007390 |doi= 10.1038/sj.onc.1207576 }}
* {{cite journal | vauthors = Gicquel C, Gaston V, Mandelbaum J, Siffroi JP, Flahault A, Le Bouc Y | title = In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene | journal = American Journal of Human Genetics | volume = 72 | issue = 5 | pages = 1338–41 | date = May 2003 | pmid = 12772698 | pmc = 1180288 | doi = 10.1086/374824 }}
*{{cite journal | author=Du M, Zhou W, Beatty LG, ''et al.'' |title=The KCNQ1OT1 promoter, a key regulator of genomic imprinting in human chromosome 11p15.5. |journal=Genomics |volume=84 |issue= 2 |pages= 288-300 |year= 2005 |pmid= 15233993 |doi= 10.1016/j.ygeno.2004.03.008 }}
* {{cite journal | vauthors = Diaz-Meyer N, Day CD, Khatod K, Maher ER, Cooper W, Reik W, Junien C, Graham G, Algar E, Der Kaloustian VM, Higgins MJ | title = Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome | journal = Journal of Medical Genetics | volume = 40 | issue = 11 | pages = 797–801 | date = November 2003 | pmid = 14627666 | pmc = 1735305 | doi = 10.1136/jmg.40.11.797 }}
*{{cite journal | author=Thakur N, Tiwari VK, Thomassin H, ''et al.'' |title=An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region. |journal=Mol. Cell. Biol. |volume=24 |issue= 18 |pages= 7855-62 |year= 2004 |pmid= 15340049 |doi= 10.1128/MCB.24.18.7855-7862.2004 }}
* {{cite journal | vauthors = Soejima H, Nakagawachi T, Zhao W, Higashimoto K, Urano T, Matsukura S, Kitajima Y, Takeuchi M, Nakayama M, Oshimura M, Miyazaki K, Joh K, Mukai T | title = Silencing of imprinted CDKN1C gene expression is associated with loss of CpG and histone H3 lysine 9 methylation at DMR-LIT1 in esophageal cancer | journal = Oncogene | volume = 23 | issue = 25 | pages = 4380–8 | date = May 2004 | pmid = 15007390 | doi = 10.1038/sj.onc.1207576 }}
*{{cite journal | author=Arima T, Kamikihara T, Hayashida T, ''et al.'' |title=ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome. |journal=Nucleic Acids Res. |volume=33 |issue= 8 |pages= 2650-60 |year= 2005 |pmid= 15888726 |doi= 10.1093/nar/gki555 }}
* {{cite journal | vauthors = Du M, Zhou W, Beatty LG, Weksberg R, Sadowski PD | title = The KCNQ1OT1 promoter, a key regulator of genomic imprinting in human chromosome 11p15.5 | journal = Genomics | volume = 84 | issue = 2 | pages = 288–300 | date = August 2004 | pmid = 15233993 | doi = 10.1016/j.ygeno.2004.03.008 }}
*{{cite journal | author=Higashimoto K, Soejima H, Saito T, ''et al.'' |title=Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer. |journal=Cytogenet. Genome Res. |volume=113 |issue= 1-4 |pages= 306-12 |year= 2006 |pmid= 16575194 |doi= 10.1159/000090846 }}
* {{cite journal | vauthors = Thakur N, Tiwari VK, Thomassin H, Pandey RR, Kanduri M, Göndör A, Grange T, Ohlsson R, Kanduri C | title = An antisense RNA regulates the bidirectional silencing property of the Kcnq1 imprinting control region | journal = Molecular and Cellular Biology | volume = 24 | issue = 18 | pages = 7855–62 | date = September 2004 | pmid = 15340049 | pmc = 515059 | doi = 10.1128/MCB.24.18.7855-7862.2004 }}
*{{cite journal | author=Geuns E, Hilven P, Van Steirteghem A, ''et al.'' |title=Methylation analysis of KvDMR1 in human oocytes. |journal=J. Med. Genet. |volume=44 |issue= 2 |pages= 144-7 |year= 2007 |pmid= 16950814 |doi= 10.1136/jmg.2006.044149 }}
* {{cite journal | vauthors = Arima T, Kamikihara T, Hayashida T, Kato K, Inoue T, Shirayoshi Y, Oshimura M, Soejima H, Mukai T, Wake N | title = ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome | journal = Nucleic Acids Research | volume = 33 | issue = 8 | pages = 2650–60 | year = 2005 | pmid = 15888726 | pmc = 1097765 | doi = 10.1093/nar/gki555 }}
*{{cite journal | author=Nakano S, Murakami K, Meguro M, ''et al.'' |title=Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers. |journal=Cancer Sci. |volume=97 |issue= 11 |pages= 1147-54 |year= 2006 |pmid= 16965397 |doi= 10.1111/j.1349-7006.2006.00305.x }}
* {{cite journal | vauthors = Higashimoto K, Soejima H, Saito T, Okumura K, Mukai T | title = Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer | journal = Cytogenetic and Genome Research | volume = 113 | issue = 1–4 | pages = 306–12 | year = 2006 | pmid = 16575194 | doi = 10.1159/000090846 }}
}}
* {{cite journal | vauthors = Geuns E, Hilven P, Van Steirteghem A, Liebaers I, De Rycke M | title = Methylation analysis of KvDMR1 in human oocytes | journal = Journal of Medical Genetics | volume = 44 | issue = 2 | pages = 144–7 | date = February 2007 | pmid = 16950814 | pmc = 2598054 | doi = 10.1136/jmg.2006.044149 }}
* {{cite journal | vauthors = Nakano S, Murakami K, Meguro M, Soejima H, Higashimoto K, Urano T, Kugoh H, Mukai T, Ikeguchi M, Oshimura M | title = Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers | journal = Cancer Science | volume = 97 | issue = 11 | pages = 1147–54 | date = November 2006 | pmid = 16965397 | doi = 10.1111/j.1349-7006.2006.00305.x }}
* {{cite journal | vauthors = Korostowski L, Sedlak N, Engel N | title = The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart | journal = PLoS Genetics | volume = 8 | issue = 9 | pages = e1002956 | date = September 2012 | pmid = 23028363 | pmc = 3447949 | doi = 10.1371/journal.pgen.1002956 }}
{{refend}}
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[[Category:Non-coding RNA]]
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Revision as of 13:19, 5 May 2017

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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.[1] 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.[2] KCNQ1OT1 is a nuclear, 91 kb transcript, found in close proximity to the nucleolus in certain cell types.[3][4]

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).[3] It plays an important role in the transcriptional silencing of the KCNQ1 locus by regulating histone methylation.[1] An 890 bp region at the 5' end of KCNQ1OT1 acts as a silencing domain.[5][6] 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.[6]

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.[7] The deletion of KCNQ1OT1 in males can result in a removal of the repressor in six cis genes.[8] Offspring from the males that had KCNQ1OT1 knocked out weighed 20-25% less than the control.[8] 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.[9] When KCNQ1OT1 transcript is truncated, normally repressed alleles on the paternal chromosome are instead expressed.[10] As the evidence shows, the misregulation of KCNQ1OT1 can lead to disastrous physical and genetic effects.

See also

References

  1. ↑ 1.0 1.1 Kanduri C (June 2011). "Kcnq1ot1: a chromatin regulatory RNA". Seminars in Cell & Developmental Biology. 22 (4): 343–50. doi:10.1016/j.semcdb.2011.02.020. PMID 21345374.
  2. ↑ 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): 1209–17. doi:10.1093/hmg/8.7.1209. PMID 10369866.
  3. ↑ 3.0 3.1 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): 232–46. doi:10.1016/j.molcel.2008.08.022. PMID 18951091.
  4. ↑ 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): 1521–8. doi:10.1534/g3.112.004226. PMC 3516474. PMID 23275875.
  5. ↑ 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): 3713–28. doi:10.1128/MCB.02263-07. PMC 2423283. PMID 18299392.
  6. ↑ 6.0 6.1 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): 2493–9. doi:10.1242/dev.048181. PMID 20573698.
  7. ↑ 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): 921–6. doi:10.1136/jmg.37.12.921. PMC 1734494. PMID 11106355.
  8. ↑ 8.0 8.1 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): 426–31. doi:10.1038/ng988. PMID 12410230.
  9. ↑ 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): 665–7. doi:10.1038/351665a0. PMID 1675767.
  10. ↑ 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): 1268–82. doi:10.1101/gad.1416906. PMC 1472902. PMID 16702402.

Further reading

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