An alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity

PLoS Genetics

Volumn 8, Issue 3, 2012, Pages

  Kuehnen, Peter ^a   Mischke, Mona ^a   Wiegand, Susanna ^a   Sers, Christine ^a   Horsthemke, Bernhard ^b   Lau, Susanne ^a   Keil, Thomas ^a   Lee, Young Ae ^a,c   Grueters, Annette ^a   Krude, Heiko ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b UNIVERSITY HOSPITAL ESSEN   (Germany)

^c MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN P300; PROOPIOMELANOCORTIN;

ADOLESCENT; ADULT; ARTICLE; BODY WEIGHT; CHILD; CHILDHOOD OBESITY; CONTROLLED STUDY; CPG ISLAND; DNA METHYLATION; EXON; FEMALE; GENE; GENE EXPRESSION; GENE LOCUS; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HUMAN; HUMAN TISSUE; INTRON; MAJOR CLINICAL STUDY; MALE; MOUSE; NONHUMAN; OBESITY; POMC GENE; PROTEIN BINDING; ALU SEQUENCE; ANIMAL; BINDING SITE; C57BL MOUSE; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETIC POLYMORPHISM; GENETICS; INFANT; METABOLISM; NEWBORN; PRESCHOOL CHILD; PRIMATE; RISK FACTOR;

ADOLESCENT; ALU ELEMENTS; ANIMALS; BINDING SITES; CHILD; CHILD, PRESCHOOL; CPG ISLANDS; DNA METHYLATION; EPIGENESIS, GENETIC; EXONS; GENE EXPRESSION REGULATION; HUMANS; INFANT; INFANT, NEWBORN; INTRONS; MICE; MICE, INBRED C57BL; OBESITY; POLYMORPHISM, GENETIC; PRIMATES; PRO-OPIOMELANOCORTIN; RISK FACTORS;

EID: 84859226938     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1002543     Document Type: Article

References (53)

1. Bjornsson HT, Fallin MD, Feinberg AP, (2004) An integrated epigenetic and genetic approach to common human disease. Trends Genet 20: 350-358.
2. Boks MP, Derks EM, Weisenberger DJ, Strengman E, Janson E, et al. (2009) The relationship of DNA methylation with age, gender and genotype in twins and healthy controls. PLoS ONE 4: e6767 doi:10.1371/journal.pone.0006767.
3. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, et al. (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 102: 10604-10609.
4. Jirtle RL, Skinner MK, (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8: 253-262.
5. Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, et al. (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299: 2877-2883.
6. Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, et al. (2009) Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev 130: 234-239.
7. Gronniger E, Weber B, Heil O, Peters N, Stab F, et al. (2010) Aging and chronic sun exposure cause distinct epigenetic changes in human skin. PLoS Genet 6: e1000971 doi:10.1371/journal.pgen.1000971.
8. Borgel J, Guibert S, Li Y, Chiba H, Schubeler D, et al. (2010) Targets and dynamics of promoter DNA methylation during early mouse development. Nat Genet 42: 1093-1100.
9. Reik W, Dean W, Walter J, (2001) Epigenetic reprogramming in mammalian development. Science 293: 1089-1093.
10. Talens RP, Boomsma DI, Tobi EW, Kremer D, Jukema JW, et al. (2010) Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J 24: 3135-3144.
11. Feinberg AP, Irizarry RA, Fradin D, Aryee MJ, Murakami P, et al. (2010) Personalized epigenomic signatures that are stable over time and covary with body mass index. Sci Transl Med 2: 49ra67.
12. Martinowich K, Hattori D, Wu H, Fouse S, He F, et al. (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302: 890-893.
13. Krude H, Biebermann H, Luck W, Horn R, Brabant G, et al. (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19: 155-157.
14. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, et al. (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet.
15. Farooqi IS, Drop S, Clements A, Keogh JM, Biernacka J, et al. (2006) Heterozygosity for a POMC-null mutation and increased obesity risk in humans. Diabetes 55: 2549-2553.
16. Takahashi H, Hakamata Y, Watanabe Y, Kikuno R, Miyata T, et al. (1983) Complete nucleotide sequence of the human corticotropin-beta-lipotropin precursor gene. Nucleic Acids Res 11: 6847-6858.
17. Lacaze-Masmonteil T, de Keyzer Y, Luton JP, Kahn A, Bertagna X, (1987) Characterization of proopiomelanocortin transcripts in human nonpituitary tissues. Proc Natl Acad Sci U S A 84: 7261-7265.
18. Gardiner-Garden M, Frommer M, (1994) Transcripts and CpG islands associated with the pro-opiomelanocortin gene and other neurally expressed genes. J Mol Endocrinol 12: 365-382.
19. Ehrlich S, Weiss D, Burghardt R, Infante-Duarte C, Brockhaus S, et al. (2010) Promoter specific DNA methylation and gene expression of POMC in acutely underweight and recovered patients with anorexia nervosa. J Psychiatr Res 44: 827-833.
20. Andersen GN, Hagglund M, Nagaeva O, Frangsmyr L, Petrovska R, et al. (2005) Quantitative measurement of the levels of melanocortin receptor subtype 1, 2, 3 and 5 and pro-opio-melanocortin peptide gene expression in subsets of human peripheral blood leucocytes. Scand J Immunol 61: 279-284.
21. Buzzetti R, McLoughlin L, Lavender PM, Clark AJ, Rees LH, (1989) Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies. J Clin Invest 83: 733-737.
22. Biebermann H, Castaneda TR, van Landeghem F, von Deimling A, Escher F, et al. (2006) A role for beta-melanocyte-stimulating hormone in human body-weight regulation. Cell Metab 3: 141-146.
23. Rolland-Cachera MF, Cole TJ, Sempe M, Tichet J, Rossignol C, et al. (1991) Body Mass Index variations: centiles from birth to 87 years. Eur J Clin Nutr 45: 13-21.
24. Bergmann RL, Bergmann KE, Lau-Schadensdorf S, Luck W, Dannemann A, et al. (1994) Atopic diseases in infancy. The German multicenter atopy study (MAS-90). Pediatr Allergy Immunol 5: 19-25.
25. Jeannotte L, Burbach JP, Drouin J, (1987) Unusual proopiomelanocortin ribonucleic acids in extrapituitary tissues: intronless transcripts in testes and long poly(A) tails in hypothalamus. Mol Endocrinol 1: 749-757.
26. Slominski A, Wortsman J, Luger T, Paus R, Solomon S, (2000) Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev 80: 979-1020.
27. Clark AJ, Lavender PM, Coates P, Johnson MR, Rees LH, (1990) In vitro and in vivo analysis of the processing and fate of the peptide products of the short proopiomelanocortin mRNA. Mol Endocrinol 4: 1737-1743.
28. Millington WR, Rosenthal DW, Unal CB, Nyquist-Battie C, (1999) Localization of pro-opiomelanocortin mRNA transcripts and peptide immunoreactivity in rat heart. Cardiovasc Res 43: 107-116.
29. Taherzadeh S, Sharma S, Chhajlani V, Gantz I, Rajora N, et al. (1999) alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages. Am J Physiol 276: R1289-1294.
30. Johansson O, Virtanen M, Hilliges M, Hansson LO, (1991) Gamma-melanocyte-stimulating hormone-like immunoreactivity in blood cells of human eosinophilic patients. Acta Haematol 86: 206-208.
31. Klug M, Rehli M, (2006) Functional analysis of promoter CpG methylation using a CpG-free luciferase reporter vector. Epigenetics 1: 127-130.
32. Liu X, Wang L, Zhao K, Thompson PR, Hwang Y, et al. (2008) The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature 451: 846-850.
33. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, et al. (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39: 311-318.
34. Chakrabarti SK, Francis J, Ziesmann SM, Garmey JC, Mirmira RG, (2003) Covalent histone modifications underlie the developmental regulation of insulin gene transcription in pancreatic beta cells. J Biol Chem 278: 23617-23623.
35. Tsukada T, Watanabe Y, Nakai Y, Imura H, Nakanishi S, et al. (1982) Repetitive DNA sequences in the human corticotropin-beta-lipotrophin precursor gene region: Alu family members. Nucleic Acids Res 10: 1471-1479.
36. Liu WM, Schmid CW, (1993) Proposed roles for DNA methylation in Alu transcriptional repression and mutational inactivation. Nucleic Acids Res 21: 1351-1359.
37. Kochanek S, Renz D, Doerfler W, (1993) DNA methylation in the Alu sequences of diploid and haploid primary human cells. EMBO J 12: 1141-1151.
38. Xing J, Witherspoon DJ, Ray DA, Batzer MA, Jorde LB, (2007) Mobile DNA elements in primate and human evolution. Am J Phys Anthropol Suppl 45: 2-19.
39. Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, et al. (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 40: 768-775.
40. Li S, Zhao JH, Luan J, Luben RN, Rodwell SA, et al. (2010) Cumulative effects and predictive value of common obesity-susceptibility variants identified by genome-wide association studies. Am J Clin Nutr 91: 184-190.
41. Newell-Price J, King P, Clark AJ, (2001) The CpG island promoter of the human proopiomelanocortin gene is methylated in nonexpressing normal tissue and tumors and represses expression. Mol Endocrinol 15: 338-348.
42. Ye L, Li X, Kong X, Wang W, Bi Y, et al. (2005) Hypomethylation in the promoter region of POMC gene correlates with ectopic overexpression in thymic carcinoids. J Endocrinol 185: 337-343.
43. Stevens A, Begum G, Cook A, Connor K, Rumball C, et al. (2010) Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition. Endocrinology 151: 3652-3664.
44. Stevens A, Begum G, White A, (2011) Epigenetic changes in the hypothalamic pro-opiomelanocortin gene: a mechanism linking maternal undernutrition to obesity in the offspring? Eur J Pharmacol 660: 194-201.
45. Plagemann A, Harder T, Brunn M, Harder A, Roepke K, et al. (2009) Hypothalamic proopiomelanocortin promoter methylation becomes altered by early overfeeding: an epigenetic model of obesity and the metabolic syndrome. J Physiol 587: 4963-4976.
46. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, et al. (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462: 315-322.
47. Li Y, Zhu J, Tian G, Li N, Li Q, et al. (2010) The DNA methylome of human peripheral blood mononuclear cells. PLoS Biol 8: e1000533 doi:10.1371/journal.pbio.1000533.
48. Muller HJ, Altenburg E, (1930) The Frequency of Translocations Produced by X-Rays in Drosophila. Genetics 15: 283-311.
49. Makino S, Kaji R, Ando S, Tomizawa M, Yasuno K, et al. (2007) Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism. Am J Hum Genet 80: 393-406.
50. Martin A, Troadec C, Boualem A, Rajab M, Fernandez R, et al. (2009) A transposon-induced epigenetic change leads to sex determination in melon. Nature 461: 1135-1138.
51. Morgan HD, Sutherland HG, Martin DI, Whitelaw E, (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23: 314-318.
52. Hajkova P, el-Maarri O, Engemann S, Oswald J, Olek A, et al. (2002) DNA-methylation analysis by the bisulfite-assisted genomic sequencing method. Methods Mol Biol 200: 143-154.
53. Kerjean A, Vieillefond A, Thiounn N, Sibony M, Jeanpierre M, et al. (2001) Bisulfite genomic sequencing of microdissected cells. Nucleic Acids Res 29: E106-106.