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Open AccessArticle

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

by Daniel Batyrev 1,2,†, Elisheva Lapid 1,3,†, Liran Carmel 1,* and Eran Meshorer 1,2,*
1
Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel
2
The Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel
3
The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this paper.
Cells 2020, 9(1), 48; https://doi.org/10.3390/cells9010048
Received: 29 October 2019 / Revised: 16 December 2019 / Accepted: 20 December 2019 / Published: 24 December 2019
(This article belongs to the Special Issue Evolution of Epigenetic Mechanisms and Signatures)
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. View Full-Text
Keywords: ancient DNA; epigenetics; DNA methylation; genome organization; gene regulation; archaic humans; comparative epigenomics ancient DNA; epigenetics; DNA methylation; genome organization; gene regulation; archaic humans; comparative epigenomics
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Batyrev, D.; Lapid, E.; Carmel, L.; Meshorer, E. Predicted Archaic 3D Genome Organization Reveals Genes Related to Head and Spinal Cord Separating Modern from Archaic Humans. Cells 2020, 9, 48.

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