KCNQ1 overlapping transcript 1, also known as KCNQ1OT1, is a

long non-coding RNA Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as mi ...

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

found in the KCNQ1

locus Locus (plural loci) is Latin for "place". It may refer to: Entertainment * Locus (comics), a Marvel Comics mutant villainess, a member of the Mutant Liberation Front * ''Locus'' (magazine), science fiction and fantasy magazine ** ''Locus Award' ...

. This locus consists of 8–10 protein-coding genes, specifically expressed from the maternal allele (including the

KCNQ1 Kv7.1 (KvLQT1) is a potassium channel protein whose primary subunit in humans is encoded by the ''KCNQ1'' gene. Kv7.1 is a voltage and lipid-gated potassium channel present in the cell membranes of cardiac tissue and in inner ear neurons among ...

gene), and the paternally expressed non-coding RNA gene KCNQ1OT1. 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 An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

and KCNQ1 is a maternally expressed allele. KCNQ1OT1 is a nuclear, 91 kb transcript, found in close proximity to the

nucleolus The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of ...

in certain cell types. It interacts with

chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...

, the histone methyltransferase G9a (responsible for the mono- and dimethylation of histone 3 lysine 9, H3K9), and the Polycomb Repressive Complex 2,

PRC2 PRC2 (polycomb repressive complex 2) is one of the two classes of polycomb-group proteins or (PcG). The other component of this group of proteins is PRC1 ( Polycomb Repressive Complex 1). This complex has histone methyltransferase activity and ...

, (responsible for the trimethylation of H3K27). It plays an important role in the

transcriptional silencing Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either Transcription (genetics), transcription or Translation (biology), translation and is often used in res ...

of the KCNQ1 locus by regulating histone methylation. An 890 bp region at the

5′ Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a single strand of DNA or RNA, the chemical convention of naming carbon atoms in the nucleotide pentose-sugar-r ...

end of KCNQ1OT1 acts as a silencing domain. 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 DNA (cytosine-5)-methyltransferase 1 is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. In humans, it is encoded by the ''DNMT1'' gene. DNMT1 forms part of the family of ...

), but does not affect the interactions of histone methyltransferases with KCNQ1OT1. 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. The deletion of KCNQ1OT1 in males can result in a removal of the repressor in six cis genes. Offspring from the males that had KCNQ1OT1 knocked out weighed 20–25% less than the control. 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. When KCNQ1OT1 transcript is truncated, normally repressed alleles on the paternal chromosome are instead expressed. As the evidence shows, the misregulation of KCNQ1OT1 can lead to disastrous physical and genetic effects.

See also

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Further reading