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Retroelement—Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution

1
I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
2
Omicsway Corp., Walnut, CA 91798, USA
3
Faculty of Biology, Moscow State University, 119192 Moscow, Russia
4
D. Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, 117198 Moscow, Russia
5
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117198 Moscow, Russia
6
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia
7
Faculty of Fundamental Medicine, Moscow State University, 119992 Moscow, Russia
8
Laboratory of the Swiss Hepato-Pancreato-Biliary (HPB) and Transplantation Center, Department of Surgery, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland
9
Program in Immunology, Sackler Graduate School, Tufts University, Boston, MA 02111, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(2), 130; https://doi.org/10.3390/cells8020130
Received: 20 December 2018 / Revised: 29 January 2019 / Accepted: 30 January 2019 / Published: 6 February 2019
(This article belongs to the Special Issue Bioinformatics and Computational Biology 2019)
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Abstract

Background: Retroelements (REs) are transposable elements occupying ~40% of the human genome that can regulate genes by providing transcription factor binding sites (TFBS). RE-linked TFBS profile can serve as a marker of gene transcriptional regulation evolution. This approach allows for interrogating the regulatory evolution of organisms with RE-rich genomes. We aimed to characterize the evolution of transcriptional regulation for human genes and molecular pathways using RE-linked TFBS accumulation as a metric. Methods: We characterized human genes and molecular pathways either enriched or deficient in RE-linked TFBS regulation. We used ENCODE database with mapped TFBS for 563 transcription factors in 13 human cell lines. For 24,389 genes and 3124 molecular pathways, we calculated the score of RE-linked TFBS regulation reflecting the regulatory evolution rate at the level of individual genes and molecular pathways. Results: The major groups enriched by RE regulation deal with gene regulation by microRNAs, olfaction, color vision, fertilization, cellular immune response, and amino acids and fatty acids metabolism and detoxication. The deficient groups were involved in translation, RNA transcription and processing, chromatin organization, and molecular signaling. Conclusion: We identified genes and molecular processes that have characteristics of especially high or low evolutionary rates at the level of RE-linked TFBS regulation in human lineage. View Full-Text
Keywords: Human genome evolution; transcription factor; retrotransposons; molecular pathways; gene ontology; ChIP-seq; omics approach in genetics Human genome evolution; transcription factor; retrotransposons; molecular pathways; gene ontology; ChIP-seq; omics approach in genetics
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Nikitin, D.; Garazha, A.; Sorokin, M.; Penzar, D.; Tkachev, V.; Markov, A.; Gaifullin, N.; Borger, P.; Poltorak, A.; Buzdin, A. Retroelement—Linked Transcription Factor Binding Patterns Point to Quickly Developing Molecular Pathways in Human Evolution. Cells 2019, 8, 130.

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