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| 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
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| 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.
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| Overall design |
DNA methylome analysis of pooled Human, Chimpanzee and Macaque
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| Contributor(s) |
Wilson GA, Woszczek G, Butcher LM, Foster HR, Feber A, Roos C, Walter L, Beck S, Bell CG |
| Citation(s) |
24598577 |
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| Submission date |
Jul 16, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Gareth Wilson |
| E-mail(s) |
gareth.wilson@ucl.ac.uk
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| Organization name |
UCL Cancer Institute
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| Street address |
23 Huntley Street
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| City |
London |
| ZIP/Postal code |
WC1E 6BT |
| Country |
United Kingdom |
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| Platforms (3) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL9160 |
Illumina Genome Analyzer II (Macaca mulatta) |
| GPL9378 |
Illumina Genome Analyzer II (Pan troglodytes) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA212356 |
| SRA |
SRP027515 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48942_RAW.tar |
203.6 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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