Human chromosomal region 11p15.5 contains two clusters of epigenetically-regulated genes that are expressed from only one chromosome in a parent-of-origin manner. Each cluster, or imprinted domain, is regulated by a functionally independent imprinting control region (ICR). The human CDKN1C/KCNQ1OT1 domain is regulated by an ICR located in an intron of KCNQ1, and contains at least eight genes that are expressed exclusively or preferentially from the maternally-inherited allele. The DNA of the ICR is specifically methylated on the maternally-inherited chromosome, and unmethylated on the paternally-inherited chromosome. The ICR contains the promoter of the KCNQ1OT1 gene that is exclusively expressed from the paternal allele. The KCNQ1OT1 transcript is the antisense to the KCNQ1 gene and is a unspliced long non-coding RNA. It interacts with chromatin and regulates transcription of multiple target genes through epigenetic modifications. The transcript is abnormally expressed from both chromosomes in most patients with Beckwith-Wiedemann syndrome, and the transcript also plays an important role in colorectal carcinogenesis. [provided by RefSeq, Apr 2012]
| OMIM ID: | `OMIM ID 604115
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Allelic Variants (Selected Examples)
.0001 BECKWITH-WIEDEMANN SYNDROME
In 2 related individuals with Beckwith-Wiedemann syndrome (BWS; 130650), Niemitz et al. (2004) described a microdeletion on 11p15 which included the entire LIT1 gene. In 1 case the deletion was maternally inherited; in the other, it was paternally inherited. In the case of maternal inheritance, the deletion caused BWS with silencing of p57(KIP2) (600859), indicating that an element important for the regulation of p57(KIP2) expression had been deleted. When inherited paternally, there was no BWS phenotype, suggesting that the LIT1 RNA itself is not necessary for normal development in humans.
Recent articles:
- Pauler FM et al. “Mechanisms of long range silencing by imprinted macro non-coding RNAs.” Curr Opin Genet Dev. 2012 Jun;22(3):283-9. PMID 22386265
- Guseva N et al. “Antisense noncoding RNA promoter regulates the timing of de novo methylation of an imprinting control region.” Dev Biol. 2012 Jan 15;361(2):403-11. PMID 22119056
- Chiesa N et al. “The KCNQ1OT1 imprinting control region and non-coding RNA: new properties derived from the study of Beckwith-Wiedemann syndrome and Silver-Russell syndrome cases.” Hum Mol Genet. 2012 Jan 1;21(1):10-25. PMID 21920939
- Saxena A et al. “Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs.” Bioessays. 2011 Nov;33(11):830-9. PMID 21915889
- Kanduri C et al. “Kcnq1ot1: a chromatin regulatory RNA.” Semin Cell Dev Biol. 2011 Jun;22(4):343-50. PMID 21345374
- Tierling S et al. “DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome.” Clin Genet. 2011 Jun;79(6):546-53. PMID 20618351
- Al-Khtib M et al. “Vitrification at the germinal vesicle stage does not affect the methylation profile of H19 and KCNQ1OT1 imprinting centers in human oocytes subsequently matured in vitro.” Fertil Steril. 2011 May;95(6):1955-60. PMID 21420679
- Shuman C et al. “Beckwith-Wiedemann Syndrome.” None 1993;. PMID 20301568
- Pick M et al. “Clone- and gene-specific aberrations of parental imprinting in human induced pluripotent stem cells.” Stem Cells. 2009 Nov;27(11):2686-90. PMID 19711451
- Mohammad F et al. “Epigenetics of imprinted long noncoding RNAs.” Epigenetics. 2009 Jul 1;4(5):277-86. PMID 19617707
Top Pubmed articles linked to gene KCNQ1OT1 matching any search term:
- Boonen SE et al. “No evidence for pathogenic variants or maternal effect of ZFP57 as the cause of Beckwith-Wiedemann Syndrome.” Eur J Hum Genet. 2012 Jan;20(1):119-21. PMID 21863059
- Demars J et al. “New insights into the pathogenesis of Beckwith-Wiedemann and Silver-Russell syndromes: contribution of small copy number variations to 11p15 imprinting defects.” Hum Mutat. 2011 Oct;32(10):1171-82. PMID 21780245
- Lin S et al. “Nonallelic transcriptional roles of CTCF and cohesins at imprinted loci.” Mol Cell Biol. 2011 Aug;31(15):3094-104. PMID 21628529
- Obata Y et al. “Epigenetically immature oocytes lead to loss of imprinting during embryogenesis.” J Reprod Dev. 2011 Jun;57(3):327-34. PMID 21289466
- Hori N et al. “Aberrant CpG methylation of the imprinting control region KvDMR1 detected in assisted reproductive technology-produced calves and pathogenesis of large offspring syndrome.” Anim Reprod Sci. 2010 Dec;122(3-4):303-12. PMID 21035970
- Hammoud SS et al. “Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility.” Fertil Steril. 2010 Oct;94(5):1728-33. PMID 19880108
- Choufani S et al. “Beckwith-Wiedemann syndrome.” Am J Med Genet C Semin Med Genet. 2010 Aug 15;154C(3):343-54. PMID 20803657
- Couldrey C et al. “DNA methylation patterns in tissues from mid-gestation bovine foetuses produced by somatic cell nuclear transfer show subtle abnormalities in nuclear reprogramming.” BMC Dev Biol. 2010 Mar 7;10:27. PMID 20205951
- Lu Y et al. “Loss of imprinting of insulin-like growth factor 2 is associated with increased risk of lymph node metastasis and gastric corpus cancer.” J Exp Clin Cancer Res. 2009 Sep 9;28:125. PMID 19737423
- Bliek J et al. “Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome.” Eur J Hum Genet. 2009 May;17(5):611-9. PMID 19092779
- Nakano S et al. “Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers.” Cancer Sci. 2006 Nov;97(11):1147-54. PMID 16965397
- Arima T et al. “ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome.” Nucleic Acids Res. 2005;33(8):2650-60. PMID 15888726
- DeBaun MR et al. “Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects.” Am J Hum Genet. 2002 Mar;70(3):604-11. PMID 11813134
- Lee MP et al. “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.” Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5203-8. PMID 10220444