Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A
The higher order organization of eukaryotic and prokaryotic genomes is pivotal in the regulation of gene expression. Specifically, chromatin accessibility in eukaryotes and nucleoid accessibility in bacteria are regulated by a cohort of proteins to alter gene expression in response to diverse physio...
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Format: | Article |
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Frontiers Media S.A.
2019-12-01
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Series: | Frontiers in Genetics |
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Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.01285/full |
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author | Dan Mishmar Rotem Levin Mansur M. Naeem Neal Sondheimer |
author_facet | Dan Mishmar Rotem Levin Mansur M. Naeem Neal Sondheimer |
author_sort | Dan Mishmar |
collection | DOAJ |
description | The higher order organization of eukaryotic and prokaryotic genomes is pivotal in the regulation of gene expression. Specifically, chromatin accessibility in eukaryotes and nucleoid accessibility in bacteria are regulated by a cohort of proteins to alter gene expression in response to diverse physiological conditions. By contrast, prior studies have suggested that the mitochondrial genome (mtDNA) is coated solely by mitochondrial transcription factor A (TFAM), whose increased cellular concentration was proposed to be the major determinant of mtDNA packaging in the mitochondrial nucleoid. Nevertheless, recent analysis of DNase-seq and ATAC-seq experiments from multiple human and mouse samples suggest gradual increase in mtDNA occupancy during the course of embryonic development to generate a conserved footprinting pattern which correlate with sites that have low TFAM occupancy in vivo (ChIP-seq) and tend to adopt G-quadruplex structures. These findings, along with recent identification of mtDNA binding by known modulators of chromatin accessibility such as MOF, suggest that mtDNA higher order organization is generated by cross talk with the nuclear regulatory system, may have a role in mtDNA regulation, and is more complex than once thought. |
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institution | Directory Open Access Journal |
issn | 1664-8021 |
language | English |
last_indexed | 2024-12-12T22:52:07Z |
publishDate | 2019-12-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Genetics |
spelling | doaj.art-430f30d2ce0c45039fa991357e0f1dd42022-12-22T00:09:02ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-12-011010.3389/fgene.2019.01285491575Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor ADan Mishmar0Rotem Levin1Mansur M. Naeem2Neal Sondheimer3Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelInstitute of Medical Sciences and the Department of Paediatrics, The University of Toronto, Toronto, ON, CanadaInstitute of Medical Sciences and the Department of Paediatrics, The University of Toronto, Toronto, ON, CanadaThe higher order organization of eukaryotic and prokaryotic genomes is pivotal in the regulation of gene expression. Specifically, chromatin accessibility in eukaryotes and nucleoid accessibility in bacteria are regulated by a cohort of proteins to alter gene expression in response to diverse physiological conditions. By contrast, prior studies have suggested that the mitochondrial genome (mtDNA) is coated solely by mitochondrial transcription factor A (TFAM), whose increased cellular concentration was proposed to be the major determinant of mtDNA packaging in the mitochondrial nucleoid. Nevertheless, recent analysis of DNase-seq and ATAC-seq experiments from multiple human and mouse samples suggest gradual increase in mtDNA occupancy during the course of embryonic development to generate a conserved footprinting pattern which correlate with sites that have low TFAM occupancy in vivo (ChIP-seq) and tend to adopt G-quadruplex structures. These findings, along with recent identification of mtDNA binding by known modulators of chromatin accessibility such as MOF, suggest that mtDNA higher order organization is generated by cross talk with the nuclear regulatory system, may have a role in mtDNA regulation, and is more complex than once thought.https://www.frontiersin.org/article/10.3389/fgene.2019.01285/fullATAC-seqDNase-seqG-quadruplexhigher order organizationmtDNAmitochondrial transcription factor A |
spellingShingle | Dan Mishmar Rotem Levin Mansur M. Naeem Neal Sondheimer Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A Frontiers in Genetics ATAC-seq DNase-seq G-quadruplex higher order organization mtDNA mitochondrial transcription factor A |
title | Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A |
title_full | Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A |
title_fullStr | Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A |
title_full_unstemmed | Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A |
title_short | Higher Order Organization of the mtDNA: Beyond Mitochondrial Transcription Factor A |
title_sort | higher order organization of the mtdna beyond mitochondrial transcription factor a |
topic | ATAC-seq DNase-seq G-quadruplex higher order organization mtDNA mitochondrial transcription factor A |
url | https://www.frontiersin.org/article/10.3389/fgene.2019.01285/full |
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