期刊论文详细信息
BMC Evolutionary Biology
Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates
Bing Su2  Yanfeng Zhang1  Xiangyu Cao1  Jinkai Wang2 
[1] Graduate School of Chinese Academy of Sciences, Beijing, People's Republic of China;State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Road, Kunming, Yunnan, 650223, People's Republic of China
关键词: Primates;    Brain evolution;    DNA methylation;   
Others  :  1140575
DOI  :  10.1186/1471-2148-12-144
 received in 2012-01-09, accepted in 2012-08-03,  发布年份 2012
PDF
【 摘 要 】

Background

The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown.

Results

To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs) in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene.

Conclusions

Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

【 授权许可】

   
2012 Wang et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150325044357767.pdf 995KB PDF download
Figure 4. 78KB Image download
Figure 3. 144KB Image download
Figure 2. 42KB Image download
Figure 1. 63KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Varki A, Altheide TK: Comparing the human and chimpanzee genomes: searching for needles in a haystack. Genome Res 2005, 15:1746-1758.
  • [2]Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC, Wilson RK, Batzer MA, Bustamante CD, Eichler EE, Hahn MW, Hardison RC, Makova KD, Miller W, Milosavljevic A, Palermo RE, Siepel A, Sikela JM, Attaway T, Bell S, Bernard KE, Buhay CJ, Chandrabose MN, Dao M, Davis C, Delehaunty KD, Ding Y, Dinh HH, Dugan-Rocha S, Fulton LA, Gabisi RA, Garner TT, Godfrey J, Hawes AC, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Kirkness EF, Cree A, Fowler RG, Lee S, Lewis LR, Li Z, Liu YS, Moore SM, Muzny D, Nazareth LV, Ngo DN, Okwuonu GO, Pai G, Parker D, Paul HA, Pfannkoch C, Pohl CS, Gibbs RA, Rogers J, Katze MG, Bumgarner R, Weinstock GM, Mardis ER, Remington KA, Strausberg RL, Venter JC, Wilson RK, Batzer MA, Bustamante CD, Eichler EE, Hahn MW, Hardison RC, Makova KD, Miller W, Milosavljevic A, Palermo RE, Siepel A, Sikela JM, Attaway T, Bell S, Bernard KE, Buhay CJ, Chandrabose MN, Dao M, Davis C, Delehaunty KD, Ding Y, Dinh HH, Dugan-Rocha S, Fulton LA, Gabisi RA, Garner TT, Godfrey J, Hawes AC, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Kirkness EF, Cree A, Fowler RG, Lee S, Lewis LR, Li Z, Liu YS, Moore SM, Muzny D, Nazareth LV, Ngo DN, Okwuonu GO, Pai G, Parker D, Paul HA, Pfannkoch C, Pohl CS, Rogers YH, Ruiz SJ, Sabo A, Santibanez J, Schneider BW, Smith SM, Sodergren E, Svatek AF, Utterback TR, Vattathil S, Warren W, White CS, Chinwalla AT, Feng Y, Halpern AL, Hillier LW, Huang X, Minx P, Nelson JO, Pepin KH, Qin X, Sutton GG, Venter E, Walenz BP, Wallis JW, Worley KC, Yang SP, Jones SM, Marra MA, Rocchi M, Schein JE, Baertsch R, Clarke L, Csuros M, Glasscock J, Harris RA, Havlak P, Jackson AR, Jiang H, Liu Y, Messina DN, Shen Y, Song HX, Wylie T, Zhang L, Birney E, Han K, Konkel MK, Lee J, Smit AF, Ullmer B, Wang H, Xing J, Burhans R, Cheng Z, Karro JE, Ma J, Raney B, She X, Cox MJ, Demuth JP, Dumas LJ, Han SG, Hopkins J, Karimpour-Fard A, Kim YH, Pollack JR, Vinar T, Addo-Quaye C, Degenhardt J, Denby A, Hubisz MJ, Indap A, Kosiol C, Lahn BT, Lawson HA, Marklein A, Nielsen R, Vallender EJ, Clark AG, Ferguson B, Hernandez RD, Hirani K, Kehrer-Sawatzki H, Kolb J, Patil S, Pu LL, Ren Y, Smith DG, Wheeler DA, Schenck I, Ball EV, Chen R, Cooper DN, Giardine B, Hsu F, Kent WJ, Lesk A, Nelson DL, O'Brien WE, Prufer K, Stenson PD, Wallace JC, Ke H, Liu XM, Wang P, Xiang AP, Yang F, Barber GP, Haussler D, Karolchik D, Kern AD, Kuhn RM, Smith KE, Zwieg AS: Evolutionary and biomedical insights from the rhesus macaque genome. Science 2007, 316:222-234.
  • [3]Khaitovich P, Hellmann I, Enard W, Nowick K, Leinweber M, Franz H, Weiss G, Lachmann M, Paabo S: Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 2005, 309:1850-1854.
  • [4]Caceres M, Lachuer J, Zapala MA, Redmond JC, Kudo L, Geschwind DH, Lockhart DJ, Preuss TM, Barlow C: Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci USA 2003, 100:13030-13035.
  • [5]Tsankova N, Renthal W, Kumar A, Nestler EJ: Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 2007, 8:355-367.
  • [6]Graff J, Mansuy IM: Epigenetic codes in cognition and behaviour. Behav Brain Res 2008, 192:70-87.
  • [7]Levenson JM, Sweatt JD: Epigenetic mechanisms in memory formation. Nat Rev Neurosci 2005, 6:108-118.
  • [8]Enard W, Fassbender A, Model F, Adorjan P, Paabo S, Olek A: Differences in DNA methylation patterns between humans and chimpanzees. Curr Biol 2004, 14:R148-R149.
  • [9]Farcas R, Schneider E, Frauenknecht K, Kondova I, Bontrop R, Bohl J, Navarro B, Metzler M, Zischler H, Zechner U, Daser A, Haaf T: Differences in DNA methylation patterns and expression of the CCRK gene in human and nonhuman primate cortices. Mol Biol Evol 2009, 26:1379-1389.
  • [10]Pai AA, Bell JT, Marioni JC, Pritchard JK, Gilad Y: A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues. PLoS Genet 2011, 7:e1001316.
  • [11]Molaro A, Hodges E, Fang F, Song Q, McCombie WR, Hannon GJ, Smith AD: Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Cell 2011, 146:1029-1041.
  • [12]Martin D, Singer M, Dhahbi J, Mao G, Zhang L, Schroth G: Pachter L. Phyloepigenomic comparison of great apes reveals a correlation between somatic and germline methylation states. Genome Res, Boffelli D; 2011.
  • [13]Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, van den Boom D: Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci USA 2005, 102:15785-15790.
  • [14]Fazzari MJ, Greally JM: Epigenomics: beyond CpG islands. Nat Rev Genet 2004, 5:446-455.
  • [15]Rakyan VK, Down TA, Thorne NP, Flicek P, Kulesha E, Graf S, Tomazou EM, Backdahl L, Johnson N, Herberth M, Howe KL, Jackson DK, Miretti MM, Fiegler H, Marioni JC, Birney E, Hubbard TJ, Carter NP, Tavare S, Beck S: An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res 2008, 18:1518-1529.
  • [16]Somel M, Franz H, Yan Z, Lorenc A, Guo S, Giger T, Kelso J, Nickel B, Dannemann M, Bahn S, Webster MJ, Weickert CS, Lachmann M, Paabo S, Khaitovich P: Transcriptional neoteny in the human brain. Proc Natl Acad Sci USA 2009, 106:5743-5748.
  • [17]Jjingo D, Conley AB, Yi S, Lunyak VV, Jordan KI: On the presence and role of human gene-body DNA methylation. Oncotarget 2012, 3:462-474.
  • [18]Down TA, Rakyan VK, Turner DJ, Flicek P, Li H, Kulesha E, Graf S, Johnson N, Herrero J, Tomazou EM, Thorne NP, Backdahl L, Herberth M, Howe KL, Jackson DK, Miretti MM, Marioni JC, Birney E, Hubbard TJ, Durbin R, Tavare S, Beck S: A Bayesian deconvolution strategy for immunoprecipitation-based DNA methylome analysis. Nat Biotechnol 2008, 26:779-785.
  • [19]Laird PW: Principles and challenges of genome-wide DNA methylation analysis. Nat Rev Genet 2010, 11:191-203.
  • [20]da Huang W, Sherman BT, Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009, 37:1-13.
  • [21]Irizarry RA, Ladd-Acosta C, Carvalho B, Wu H, Brandenburg SA, Jeddeloh JA, Wen B, Feinberg AP: Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res 2008, 18:780-790.
  • [22]Bock C, Tomazou EM, Brinkman AB, Muller F, Simmer F, Gu H, Jager N, Gnirke A, Stunnenberg HG, Meissner A: Quantitative comparison of genome-wide DNA methylation mapping technologies. Nat Biotechnol 2010, 28:1106-1114.
  • [23]Ehrich M, Turner J, Gibbs P, Lipton L, Giovanneti M, Cantor C, van den Boom D: Cytosine methylation profiling of cancer cell lines. Proc Natl Acad Sci USA 2008, 105:4844-4849.
  • [24]Kronig H, Riedel M, Schwarz MJ, Strassnig M, Moller HJ, Ackenheil M, Muller N: ICAM G241A polymorphism and soluble ICAM-1 serum levels: evidence for an active immune process in schizophrenia. Neuroimmunomodulation 2005, 12:54-59.
  • [25]Pola R, Flex A, Gaetani E, Santoliquido A, Serricchio M, Pola P, Bernabei R: Intercellular adhesion molecule-1 K469E gene polymorphism and Alzheimer's disease. Neurobiol Aging 2003, 24:385-387.
  • [26]Wendholt D, Spilker C, Schmitt A, Dolnik A, Smalla KH, Proepper C, Bockmann J, Sobue K, Gundelfinger ED, Kreutz MR, Boeckers TM: ProSAP-interacting protein 1 (ProSAPiP1), a novel protein of the postsynaptic density that links the spine-associated Rap-Gap (SPAR) to the scaffolding protein ProSAP2/Shank3. J Biol Chem 2006, 281:13805-13816.
  • [27]Langbein L, Rogers MA, Praetzel S, Winter H, Schweizer J: K6irs1, K6irs2, K6irs3, and K6irs4 represent the inner-root-sheath-specific type II epithelial keratins of the human hair follicle. J Invest Dermatol 2003, 120:512-522.
  • [28]Bock C, Walter J, Paulsen M, Lengauer T: Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping. Nucleic Acids Res 2008, 36:e55.
  • [29]Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP: The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 2009, 41:178-186.
  • [30]Yagi S, Hirabayashi K, Sato S, Li W, Takahashi Y, Hirakawa T, Wu G, Hattori N, Ohgane J, Tanaka S, Liu XS, Shiota K: DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression. Genome Res 2008, 18:1969-1978.
  • [31]Jurka J, Zietkiewicz E, Labuda D: Ubiquitous mammalian-wide interspersed repeats (MIRs) are molecular fossils from the mesozoic era. Nucleic Acids Res 1995, 23:170-175.
  • [32]Ball MP, Li JB, Gao Y, Lee JH, LeProust EM, Park IH, Xie B, Daley GQ, Church GM: Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol 2009, 27:361-368.
  • [33]Jirtle RL, Skinner MK: Environmental epigenomics and disease susceptibility. Nat Rev Genet 2007, 8:253-262.
  • [34]Rakyan VK, Beck S: Epigenetic variation and inheritance in mammals. Curr Opin Genet Dev 2006, 16:573-577.
  • [35]Richards EJ: Inherited epigenetic variation–revisiting soft inheritance. Nat Rev Genet 2006, 7:395-401.
  • [36]Kerkel K, Spadola A, Yuan E, Kosek J, Jiang L, Hod E, Li K, Murty VV, Schupf N, Vilain E, Morris M, Haghighi F, Tycko B: Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation. Nat Genet 2008, 40:904-908.
  • [37]Schalkwyk LC, Meaburn EL, Smith R, Dempster EL, Jeffries AR, Davies MN, Plomin R, Mill J: Allelic skewing of DNA methylation is widespread across the genome. Am J Hum Genet 2010, 86:196-212.
  • [38]Zhang D, Cheng L, Badner JA, Chen C, Chen Q, Luo W, Craig DW, Redman M, Gershon ES, Liu C: Genetic control of individual differences in gene-specific methylation in human brain. Am J Hum Genet 2010, 86:411-419.
  • [39]Mathieu O, Bender J: RNA-directed DNA methylation. J Cell Sci. 2004, 117:4881-4888.
  • [40]Zaratiegui M, Irvine DV, Martienssen RA: Noncoding RNAs and gene silencing. Cell 2007, 128:763-776.
  • [41]Mattick JS, Amaral PP, Dinger ME, Mercer TR, Mehler MF: RNA regulation of epigenetic processes. Bioessays 2009, 31:51-59.
  • [42]Ponting CP, Oliver PL, Reik W: Evolution and functions of long noncoding RNAs. Cell 2009, 136:629-641.
  • [43]Shoemaker R, Deng J, Wang W, Zhang K: Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. Genome Res 2010, 20:883-889.
  • [44]Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, Reik W: Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 2003, 35:88-93.
  • [45]Silva AJ, White R: Inheritance of allelic blueprints for methylation patterns. Cell 1988, 54:145-152.
  • [46]Ottinger MA, Maltison JA, Zelinski MB, Wu JM, Kohama SG, Roth GS, Lane MA, Ingram DK: The rhesus macaque as a model of human aging and age-related disease. In Handbook of models for human aging. Volume 1. Edited by Conn PM. Elservier Inc, Burlinglon; 2006:457-464.
  • [47]Smyth GK: Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 2004, 3:Article3.
  • [48]Bock C, Reither S, Mikeska T, Paulsen M, Walter J, Lengauer T: BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics 2005, 21:4067-4068.
  文献评价指标  
  下载次数:5次 浏览次数:3次