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Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans

High coverage sequences of archaic humans enabled the reconstruction of their DNA methylation patterns. This allowed comparing gene regulation between human groups, and linking such regulatory changes to phenotypic differences. In a previous work, a detailed comparison of DNA methylation in modern h...

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Autores principales: Batyrev, Daniel, Lapid, Elisheva, Carmel, Liran, Meshorer, Eran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017363/
https://www.ncbi.nlm.nih.gov/pubmed/31878147
http://dx.doi.org/10.3390/cells9010048
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author Batyrev, Daniel
Lapid, Elisheva
Carmel, Liran
Meshorer, Eran
author_facet Batyrev, Daniel
Lapid, Elisheva
Carmel, Liran
Meshorer, Eran
author_sort Batyrev, Daniel
collection PubMed
description High coverage sequences of archaic humans enabled the reconstruction of their DNA methylation patterns. This allowed comparing gene regulation between human groups, and linking such regulatory changes to phenotypic differences. In a previous work, a detailed comparison of DNA methylation in modern humans, archaic humans, and chimpanzees revealed 873 modern human-derived differentially methylated regions (DMRs). To understand the regulatory implications of these DMRs, we defined differentially methylated genes (DMGs) as genes that harbor DMRs in their promoter or gene body. While most of the modern human-derived DMRs could be linked to DMGs, many others remained unassigned. Here, we used information on 3D genome organization to link ~70 out of the remaining 288 unassigned DMRs to genes. Combined with the previously identified DMGs, we reinforce the enrichment of these genes with vocal and facial anatomy, and additionally find significant enrichment with the spinal column, chin, hair, and scalp. These results reveal the importance of 3D genomic organization in understanding gene regulation by DNA methylation.
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spelling pubmed-70173632020-02-28 Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans Batyrev, Daniel Lapid, Elisheva Carmel, Liran Meshorer, Eran Cells Article High coverage sequences of archaic humans enabled the reconstruction of their DNA methylation patterns. This allowed comparing gene regulation between human groups, and linking such regulatory changes to phenotypic differences. In a previous work, a detailed comparison of DNA methylation in modern humans, archaic humans, and chimpanzees revealed 873 modern human-derived differentially methylated regions (DMRs). To understand the regulatory implications of these DMRs, we defined differentially methylated genes (DMGs) as genes that harbor DMRs in their promoter or gene body. While most of the modern human-derived DMRs could be linked to DMGs, many others remained unassigned. Here, we used information on 3D genome organization to link ~70 out of the remaining 288 unassigned DMRs to genes. Combined with the previously identified DMGs, we reinforce the enrichment of these genes with vocal and facial anatomy, and additionally find significant enrichment with the spinal column, chin, hair, and scalp. These results reveal the importance of 3D genomic organization in understanding gene regulation by DNA methylation. MDPI 2019-12-24 /pmc/articles/PMC7017363/ /pubmed/31878147 http://dx.doi.org/10.3390/cells9010048 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Batyrev, Daniel
Lapid, Elisheva
Carmel, Liran
Meshorer, Eran
Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans
title Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans
title_full Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans
title_fullStr Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans
title_full_unstemmed Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans
title_short Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans
title_sort predicted archaic 3d genome organization reveals genes related to head and spinal cord separating modern from archaic humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017363/
https://www.ncbi.nlm.nih.gov/pubmed/31878147
http://dx.doi.org/10.3390/cells9010048
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