Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β-cell mass by epigenetic modification of Cdkn1c

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 27, 2015, Pages 8332-8337

  Asahara, Shun Ichiro ^a   Etoh, Hiroaki ^a   Inoue, Hiroyuki ^a   Teruyama, Kyoko ^a   Shibutani, Yuki ^a   Ihara, Yuka ^a   Kawada, Yukina ^a   Bartolome, Alberto ^a   Hashimoto, Naoko ^a   Matsuda, Tomokazu ^a   Koyanagi Kimura, Maki ^a   Kanno, Ayumi ^a   Hirota, Yushi ^a   Hosooka, Tetsuya ^a   Nagashima, Kazuaki ^b   Nishimura, Wataru ^c   Inoue, Hiroshi ^d   Matsumoto, Michihiro ^e   Higgins, Michael J ^f   Yasuda, Kazuki ^e   Inagaki, Nobuya ^b   Seino, Susumu ^a   Kasuga, Masato ^e   Kido, Yoshiaki ^a   Kahn, C Ronald ^g   more..

^a KOBE UNIVERSITY   (Japan)

^b KYOTO UNIVERSITY   (Japan)

^c JICHI MEDICAL UNIVERSITY   (Japan)

^d KANAZAWA UNIVERSITY   (Japan)

^e NATIONAL CENTER FOR GLOBAL HEALTH AND MEDICINE   (Japan)

^f ROSWELL PARK CANCER INSTITUTE   (United States)

^g HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Imprinting; Kcnq1; Pancreatic cells

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1C; INSULIN; MESSENGER RNA; POTASSIUM CHANNEL KCNQ1; UNTRANSLATED RNA; CDKN1C PROTEIN, MOUSE; GLUCOSE; KCNQ1 PROTEIN, MOUSE;

ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CHROMOSOME 7; CONTROLLED STUDY; EPIGENETICS; GENE LOCUS; GENOME IMPRINTING; IMPAIRED GLUCOSE TOLERANCE; INSULIN RELEASE; KNOCKOUT MOUSE; METABOLIC PARAMETERS; MOUSE; MUTATION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ANIMAL; BLOOD; DRUG EFFECTS; GENE EXPRESSION; GENETIC EPIGENESIS; GENETICS; GLUCOSE TOLERANCE TEST; IMMUNOBLOTTING; INHERITANCE; MALE; METABOLISM; SECRETION (PROCESS);

MUS;

ALLELES; ANIMALS; CYCLIN-DEPENDENT KINASE INHIBITOR P57; EPIGENESIS, GENETIC; GENE EXPRESSION; GENOMIC IMPRINTING; GLUCOSE; GLUCOSE TOLERANCE TEST; IMMUNOBLOTTING; INHERITANCE PATTERNS; INSULIN; INSULIN-SECRETING CELLS; KCNQ1 POTASSIUM CHANNEL; MALE; MICE, KNOCKOUT; MUTATION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 84936804492     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1422104112     Document Type: Article

References (43)

1. Voight BF, et al.; MAGIC investigators; GIANT Consortium (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 42(7):579-589.
2. Yamauchi T, et al. (2010) A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Nat Genet 42(10):864-868.
3. Yasuda K, et al. (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 40(9):1092-1097.
4. Unoki H, et al. (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 40(9):1098-1102.
5. Chen YH, et al. (2003) KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science 299(5604):251-254.
6. Wang Q, et al. (1996) Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 12(1):17-23.
7. Grahammer F, et al. (2001) The cardiac K+ channel KCNQ1 is essential for gastric acid secretion. Gastroenterology 120(6):1363-1371.
8. Grahammer F, Warth R, Barhanin J, Bleich M, Hug MJ (2001) The small conductance K+ channel, KCNQ1: Expression, function, and subunit composition in murine trachea. J Biol Chem 276(45):42268-42275.
9. Hu C, et al. (2009) Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia 52(7):1322-1325.
10. Jonsson A, et al. (2009) A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired insulin secretion. Diabetes 58(10):2409-2413.
11. Kong A, et al.; DIAGRAM Consortium (2009) Parental origin of sequence variants associated with complex diseases. Nature 462(7275):868-874.
12. Casimiro MC, et al. (2001) Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome. Proc Natl Acad Sci USA 98(5):2526-2531.
13. Lee MP, Hu RJ, Johnson LA, Feinberg AP (1997) Human KVLQT1 gene shows tissue specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements. Nat Genet 15(2):181-185.
14. Gould TD, Pfeifer K (1998) Imprinting of mouse Kvlqt1 is developmentally regulated. Hum Mol Genet 7(3):483-487.
15. Caspary T, Cleary MA, Baker CC, Guan XJ, Tilghman SM (1998) Multiple mechanisms regulate imprinting of the mouse distal chromosome 7 gene cluster. Mol Cell Biol 18(6):3466-3474.
16. Smilinich NJ, et al. (1999) 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 USA 96(14):8064-8069.
17. Fitzpatrick GV, Soloway PD, Higgins MJ (2002) Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet 32(3):426-431.
18. Shin JY, Fitzpatrick GV, Higgins MJ (2008) Two distinct mechanisms of silencing by the KvDMR1 imprinting control region. EMBO J 27(1):168-178.
19. Pandey RR, et al. (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32(2):232-246.
20. Matsuoka S, et al. (1995) p57KIP2, a structurally distinct member of the p21CIP1 Cdk inhibitor family, is a candidate tumor suppressor gene. Genes Dev 9(6):650-662.
21. Mohammad F, Mondal T, Guseva N, Pandey GK, Kanduri C (2010) Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development 137(15):2493-2499.
22. Redrup L, et al. (2009) The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development 136(4):525-530.
23. Yang X, et al. (2009) CDKN1C (p57) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cells. PLoS ONE 4(4):e5011.
24. Mancini-Dinardo D, Steele SJ, Levorse JM, Ingram RS, Tilghman SM (2006) Elongation of the Kcnq1ot1 transcript is required for genomic imprinting of neighboring genes. Genes Dev 20(10):1268-1282.
25. Jacobson DA, et al. (2007) Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing insulin secretion. Cell Metab 6(3):229-235.
26. MacDonald PE, Wheeler MB (2003) Voltage-dependent K(+) channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets. Diabetologia 46(8): 1046-1062.
27. Rosengren AH, et al. (2012) Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes. Diabetes 61(7):1726-1733.
28. Torekov SS, et al. (2014) KCNQ1 long QT syndrome patients have hyperinsulinemia and symptomatic hypoglycemia. Diabetes 63(4):1315-1325.
29. Barrès R, et al. (2009) Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density. Cell Metab 10(3):189-198.
30. Chen H, et al. (2009) Polycomb protein Ezh2 regulates pancreatic beta-cell Ink4a/Arf expression and regeneration in diabetes mellitus. Genes Dev 23(8):975-985.
31. Park JH, Stoffers DA, Nicholls RD, Simmons RA (2008) Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 118(6):2316-2324.
32. Travers ME, et al. (2013) Insights into the molecular mechanism for type 2 diabetes susceptibility at the KCNQ1 locus from temporal changes in imprinting status in human islets. Diabetes 62(3):987-992.
33. Avrahami D, et al. (2014) Targeting the cell cycle inhibitor p57Kip2 promotes adult human β cell replication. J Clin Invest 124(2):670-674.
34. Kassem SA, et al. (2001) p57(KIP2) expression in normal islet cells and in hyperinsulinism of infancy. Diabetes 50(12):2763-2769.
35. Ohshige T, et al. (2011) Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese. PLoS ONE 6(10):e26911.
36. Mahajan A, et al.; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D) Consortium; Mexican American Type 2 Diabetes (MAT2D) Consortium; Type 2 Diabetes Genetic Exploration by Nexgeneration sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium (2014) Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet 46(3):234-244.
37. Fadista J, et al. (2014) Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism. Proc Natl Acad Sci USA 111(38):13924-13929.
38. Shigeyama Y, et al. (2008) Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice. Mol Cell Biol 28(9):2971-2979.
39. Hashimoto N, et al. (2006) Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass. Nat Genet 38(5):589-593.
40. Matsuda T, et al. (2010) Ablation of C/EBPbeta alleviates ER stress and pancreatic beta cell failure through the GRP78 chaperone in mice. J Clin Invest 120(1):115-126.
41. Tudurí E, Filiputti E, Carneiro EM, Quesada I (2008) Inhibition of Ca2+ signaling and glucagon secretion in mouse pancreatic alpha-cells by extracellular ATP and purinergic receptors. Am J Physiol Endocrinol Metab 294(5):E952-E960.
42. Asahara S, et al. (2013) Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin. Diabetologia 56(5): 1088-1097.
43. Miki T, et al. (2005) Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility. Diabetes 54(4): 1056-1063.