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Series GSE48942 Query DataSets for GSE48942
Status Public on Feb 01, 2014
Title Compararitve Triprimate Peripheral Blood DNA Methylome
Organisms Macaca mulatta; Pan troglodytes; Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary DNA methylation is critical for development and is strongly associated with gene regulation. Variation in the DNA methylome between closely related species may reveal unique functional adaptation. We have implemented a novel inter-primate DNA methylation genome-wide analysis between human, chimpanzee and rhesus macaque to identify human species-specific Differentially Methylated Regions (human s-DMRs) in orthologous loci. We analysed the peripheral blood cell DNA methylomes of these primates and identified 22,758 hypomethylated and 15,858 hypermethylated human s-DMRs. These s-DMRs are globally enriched within weak promoter, enhancer and transcribed regions via comparison with ChromHMM segmentation. Human s-DMRs, (both hypo- and hypermethylated) are found to be more prevalent in CpG Island shores than within the islands themselves (?2 P = 1.80 x 10-32). Examining human-specific Transcription Factor Binding Site motif change within CpG islands, we show gain and loss, in hypomethylated and hypermethylated s-DMRs, respectively, of CTCF motifs. Epigenetically the most divergent human-specific locus was the immunological Leukotriene B4 receptor (LTB4R, aka BLT1 receptor), due to collocating hypomethylated s-DMRs within the promoter CpG island and shore, as well as inverse increased gene body methylation. This gene is vital in host immune responses and associated with the pathogenesis of a wide range of human inflammatory diseases. This finding was supported by additional neutrophil-only DNA methylome and lymphoblastoid H3K4me3 chromatin comparative data. Functional investigation of the consequences of these epigenetic differences identified this receptor to have increased expression, and have a higher response to the LTB4 ligand in human versus rhesus macaque peripheral blood mononuclear cells. This result further emphasises the exclusive nature of the human immunological system, its divergent adaptation even from closely related primates, and the power of comparative epigenomics to identify and understand human uniqueness.
 
Overall design DNA methylome analysis of pooled Human, Chimpanzee and Macaque
 
Contributor(s) Wilson GA, Woszczek G, Butcher LM, Foster HR, Feber A, Roos C, Walter L, Beck S, Bell CG
Citation(s) 24598577
Submission date Jul 16, 2013
Last update date May 15, 2019
Contact name Gareth Wilson
E-mail(s) gareth.wilson@ucl.ac.uk
Organization name UCL Cancer Institute
Street address 23 Huntley Street
City London
ZIP/Postal code WC1E 6BT
Country United Kingdom
 
Platforms (3)
GPL9115 Illumina Genome Analyzer II (Homo sapiens)
GPL9160 Illumina Genome Analyzer II (Macaca mulatta)
GPL9378 Illumina Genome Analyzer II (Pan troglodytes)
Samples (3)
GSM1187198 Human_MeDIP
GSM1187199 Chimpanzee_MeDIP
GSM1187200 Macaca_MeDIP
Relations
BioProject PRJNA212356
SRA SRP027515

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Supplementary file Size Download File type/resource
GSE48942_RAW.tar 203.6 Mb (http)(custom) TAR (of BED, BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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