Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Methylome Analysis of FF HPV+ and HPV- HNSCC samples

ABSTRACT: The analysis of the 6 methylomes by MeDIP-Seq comprise 3 HPV+ HNSCC samples and 3 HPV- HNSCC samples Analysis of the 6 methylomes, comprising 3 HPV+ HNSCC samples and 3 HPV- HNSCC samples

ORGANISM(S): Homo sapiens

SUBMITTER: Gareth Wilson

PROVIDER: E-GEOD-38263 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.

Lechner Matthias M Fenton Tim T West James J Wilson Gareth G Feber Andrew A Henderson Stephen S Thirlwell Christina C Dibra Harpreet K HK Jay Amrita A Butcher Lee L Chakravarthy Ankur R AR Gratrix Fiona F Patel Nirali N Vaz Francis F O'Flynn Paul P Kalavrezos Nicholas N Teschendorff Andrew E AE Boshoff Chris C Beck Stephan S

Genome medicine 20130205 2

<h4>Background</h4>Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA-methylation analysis.<h4>Methods</h4>Using laser-capture microdissection of 42 formalin-fixed paraffin wax-embedded (FFPE) HNSCCs, we generated DNA-methylation profiles of 18 HPV+ and 14 HPV ...[more]

PMID: 23419152

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Project description: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. DNA methylome analysis of pooled Human, Chimpanzee and Macaque

Dataset Information

Methylome Analysis of FF HPV+ and HPV- HNSCC samples

Publications

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.

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