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A common pattern of DNase-I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization

Amit Blumberg, View ORCID ProfileCharles G. Danko, View ORCID ProfileAnshul Kundaje, View ORCID ProfileDan Mishmar
doi: https://doi.org/10.1101/193037
Amit Blumberg
1Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, 84105 Israel.
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Charles G. Danko
2Baker Institute for Animal Health, Cornell University, Ithaca, New York, 14853, USA.
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Anshul Kundaje
3Department of Genetics, Stanford University, Stanford, California, 94305-5120, USA.
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Dan Mishmar
1Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, 84105 Israel.
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  • ORCID record for Dan Mishmar
  • For correspondence: dmishmar@bgu.ac.il
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Abstract

Human mitochondrial DNA (mtDNA) is believed to lack chromatin and histones. Instead, it is coated solely by the transcription factor TFAM, which binds the mtDNA without sequence specificity and packs it into a bacterial-like nucleoid in a dose-dependent fashion. We asked whether mtDNA packaging is more regulated than once thought. As a first step to address this question, we analyzed mtDNA DNase-I-seq experiments in 324 different human cell types and found, for the first time, a pattern of 29 Genomic footprinting (DGF) sites throughout the mtDNA shared by ∼90% of the tested samples. Low SNP density at the DGF sites, and their conservation in mouse DNase-seq experiments, reflect strong selective constraints. Co-localization of the DGFs with known mtDNA regulatory elements and with recently-discovered transcription pausing sites, suggest a role for such DGFs in mtDNA transcription. Altered mtDNA DGF pattern in IL-3 treated CD+34 cells offer first clue to their physiological importance. Taken together, human mtDNA has a conserved and regulated protein-DNA organization, which is likely involved in regulation of mtDNA gene expression.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 23, 2017.
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A common pattern of DNase-I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization
Amit Blumberg, Charles G. Danko, Anshul Kundaje, Dan Mishmar
bioRxiv 193037; doi: https://doi.org/10.1101/193037
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A common pattern of DNase-I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization
Amit Blumberg, Charles G. Danko, Anshul Kundaje, Dan Mishmar
bioRxiv 193037; doi: https://doi.org/10.1101/193037

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