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Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta
DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989156/ https://www.ncbi.nlm.nih.gov/pubmed/29376485 http://dx.doi.org/10.1080/15592294.2018.1429857 |
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author | Gong, Sungsam Johnson, Michelle D Dopierala, Justyna Gaccioli, Francesca Sovio, Ulla Constância, Miguel Smith, Gordon CS Charnock-Jones, D Stephen |
author_facet | Gong, Sungsam Johnson, Michelle D Dopierala, Justyna Gaccioli, Francesca Sovio, Ulla Constância, Miguel Smith, Gordon CS Charnock-Jones, D Stephen |
author_sort | Gong, Sungsam |
collection | PubMed |
description | DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome oxidative bisulfite sequencing in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. Most highly ranked differentially methylated regions (DMRs) were located on the X chromosome but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi Multiple Domains 1 (CSMD1) gene on chromosome 8. The sex-specific differential methylation pattern observed in this region was validated in additional placentas using in-solution target capture. In a new RNA-seq data set from 64 female and 67 male placentas, CSMD1 mRNA was 1.8-fold higher in male than in female placentas (P value = 8.5 × 10(−7), Mann-Whitney test). Exon-level quantification of CSMD1 mRNA from these 131 placentas suggested a likely placenta-specific CSMD1 isoform not detected in the 21 somatic tissues analyzed. We show that the gene body of an autosomal gene, CSMD1, is differentially methylated in a sex- and placental-specific manner, displaying sex-specific differences in placental transcript abundance. |
format | Online Article Text |
id | pubmed-5989156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-59891562018-06-14 Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta Gong, Sungsam Johnson, Michelle D Dopierala, Justyna Gaccioli, Francesca Sovio, Ulla Constância, Miguel Smith, Gordon CS Charnock-Jones, D Stephen Epigenetics Research Articles DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome oxidative bisulfite sequencing in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. Most highly ranked differentially methylated regions (DMRs) were located on the X chromosome but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi Multiple Domains 1 (CSMD1) gene on chromosome 8. The sex-specific differential methylation pattern observed in this region was validated in additional placentas using in-solution target capture. In a new RNA-seq data set from 64 female and 67 male placentas, CSMD1 mRNA was 1.8-fold higher in male than in female placentas (P value = 8.5 × 10(−7), Mann-Whitney test). Exon-level quantification of CSMD1 mRNA from these 131 placentas suggested a likely placenta-specific CSMD1 isoform not detected in the 21 somatic tissues analyzed. We show that the gene body of an autosomal gene, CSMD1, is differentially methylated in a sex- and placental-specific manner, displaying sex-specific differences in placental transcript abundance. Taylor & Francis 2018-02-21 /pmc/articles/PMC5989156/ /pubmed/29376485 http://dx.doi.org/10.1080/15592294.2018.1429857 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Gong, Sungsam Johnson, Michelle D Dopierala, Justyna Gaccioli, Francesca Sovio, Ulla Constância, Miguel Smith, Gordon CS Charnock-Jones, D Stephen Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta |
title | Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta |
title_full | Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta |
title_fullStr | Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta |
title_full_unstemmed | Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta |
title_short | Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta |
title_sort | genome-wide oxidative bisulfite sequencing identifies sex-specific methylation differences in the human placenta |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989156/ https://www.ncbi.nlm.nih.gov/pubmed/29376485 http://dx.doi.org/10.1080/15592294.2018.1429857 |
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