Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing
Imprinting is a critical part of normal embryonic development in mammals, controlled by defined parent-of-origin (PofO) differentially methylated regions (DMRs) known as imprinting control regions. Direct nanopore sequencing of DNA provides a means to detect allelic methylation and to overcome the d...
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| Format: | Article |
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eLife Sciences Publications Ltd
2022-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/77898 |
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| author | Vahid Akbari Jean-Michel Garant Kieran O'Neill Pawan Pandoh Richard Moore Marco A Marra Martin Hirst Steven JM Jones |
| author_facet | Vahid Akbari Jean-Michel Garant Kieran O'Neill Pawan Pandoh Richard Moore Marco A Marra Martin Hirst Steven JM Jones |
| author_sort | Vahid Akbari |
| collection | DOAJ |
| description | Imprinting is a critical part of normal embryonic development in mammals, controlled by defined parent-of-origin (PofO) differentially methylated regions (DMRs) known as imprinting control regions. Direct nanopore sequencing of DNA provides a means to detect allelic methylation and to overcome the drawbacks of methylation array and short-read technologies. Here, we used publicly available nanopore sequencing data for 12 standard B-lymphocyte cell lines to acquire the genome-wide mapping of imprinted intervals in humans. Using the sequencing data, we were able to phase 95% of the human methylome and detect 94% of the previously well-characterized, imprinted DMRs. In addition, we found 42 novel imprinted DMRs (16 germline and 26 somatic), which were confirmed using whole-genome bisulfite sequencing (WGBS) data. Analysis of WGBS data in mouse (Mus musculus), rhesus monkey (Macaca mulatta), and chimpanzee (Pan troglodytes) suggested that 17 of these imprinted DMRs are conserved. Some of the novel imprinted intervals are within or close to imprinted genes without a known DMR. We also detected subtle parental methylation bias, spanning several kilobases at seven known imprinted clusters. At these blocks, hypermethylation occurs at the gene body of expressed allele(s) with mutually exclusive H3K36me3 and H3K27me3 allelic histone marks. These results expand upon our current knowledge of imprinting and the potential of nanopore sequencing to identify imprinting regions using only parent-offspring trios, as opposed to the large multi-generational pedigrees that have previously been required. |
| first_indexed | 2024-04-14T07:38:15Z |
| format | Article |
| id | doaj.art-1088926dbaf64c879577b7d74c27db85 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:38:15Z |
| publishDate | 2022-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1088926dbaf64c879577b7d74c27db852022-12-22T02:05:37ZengeLife Sciences Publications LtdeLife2050-084X2022-07-011110.7554/eLife.77898Genome-wide detection of imprinted differentially methylated regions using nanopore sequencingVahid Akbari0https://orcid.org/0000-0001-8005-7776Jean-Michel Garant1Kieran O'Neill2https://orcid.org/0000-0001-7609-5905Pawan Pandoh3Richard Moore4Marco A Marra5https://orcid.org/0000-0001-7146-7175Martin Hirst6Steven JM Jones7https://orcid.org/0000-0003-3394-2208Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, CanadaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, CanadaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, CanadaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, CanadaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, CanadaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, CanadaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada; Department of Microbiology and Immunology, Michael Smith Laboratories, University of British Columbia, Vancouver, CanadaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, CanadaImprinting is a critical part of normal embryonic development in mammals, controlled by defined parent-of-origin (PofO) differentially methylated regions (DMRs) known as imprinting control regions. Direct nanopore sequencing of DNA provides a means to detect allelic methylation and to overcome the drawbacks of methylation array and short-read technologies. Here, we used publicly available nanopore sequencing data for 12 standard B-lymphocyte cell lines to acquire the genome-wide mapping of imprinted intervals in humans. Using the sequencing data, we were able to phase 95% of the human methylome and detect 94% of the previously well-characterized, imprinted DMRs. In addition, we found 42 novel imprinted DMRs (16 germline and 26 somatic), which were confirmed using whole-genome bisulfite sequencing (WGBS) data. Analysis of WGBS data in mouse (Mus musculus), rhesus monkey (Macaca mulatta), and chimpanzee (Pan troglodytes) suggested that 17 of these imprinted DMRs are conserved. Some of the novel imprinted intervals are within or close to imprinted genes without a known DMR. We also detected subtle parental methylation bias, spanning several kilobases at seven known imprinted clusters. At these blocks, hypermethylation occurs at the gene body of expressed allele(s) with mutually exclusive H3K36me3 and H3K27me3 allelic histone marks. These results expand upon our current knowledge of imprinting and the potential of nanopore sequencing to identify imprinting regions using only parent-offspring trios, as opposed to the large multi-generational pedigrees that have previously been required.https://elifesciences.org/articles/77898imprintingnanopore sequencingallele-specific methylationDNA methylationH3K36me3H3K27me3 |
| spellingShingle | Vahid Akbari Jean-Michel Garant Kieran O'Neill Pawan Pandoh Richard Moore Marco A Marra Martin Hirst Steven JM Jones Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing eLife imprinting nanopore sequencing allele-specific methylation DNA methylation H3K36me3 H3K27me3 |
| title | Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing |
| title_full | Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing |
| title_fullStr | Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing |
| title_full_unstemmed | Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing |
| title_short | Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing |
| title_sort | genome wide detection of imprinted differentially methylated regions using nanopore sequencing |
| topic | imprinting nanopore sequencing allele-specific methylation DNA methylation H3K36me3 H3K27me3 |
| url | https://elifesciences.org/articles/77898 |
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