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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255983/ https://www.ncbi.nlm.nih.gov/pubmed/35787786 http://dx.doi.org/10.7554/eLife.77898 |
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author | Akbari, Vahid Garant, Jean-Michel O'Neill, Kieran Pandoh, Pawan Moore, Richard Marra, Marco A Hirst, Martin Jones, Steven JM |
author_facet | Akbari, Vahid Garant, Jean-Michel O'Neill, Kieran Pandoh, Pawan Moore, Richard Marra, Marco A Hirst, Martin Jones, Steven JM |
author_sort | Akbari, Vahid |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9255983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-92559832022-07-06 Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing Akbari, Vahid Garant, Jean-Michel O'Neill, Kieran Pandoh, Pawan Moore, Richard Marra, Marco A Hirst, Martin Jones, Steven JM eLife Computational and Systems Biology 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. eLife Sciences Publications, Ltd 2022-07-05 /pmc/articles/PMC9255983/ /pubmed/35787786 http://dx.doi.org/10.7554/eLife.77898 Text en © 2022, Akbari et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Akbari, Vahid Garant, Jean-Michel O'Neill, Kieran Pandoh, Pawan Moore, Richard Marra, Marco A Hirst, Martin Jones, Steven JM Genome-wide detection of imprinted differentially methylated regions using nanopore sequencing |
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 | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255983/ https://www.ncbi.nlm.nih.gov/pubmed/35787786 http://dx.doi.org/10.7554/eLife.77898 |
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