A common pattern of DNase I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization
Human mitochondrial DNA (mtDNA) is believed to lack chromatin and histones. Instead, it is coated solely by the transcription factor TFAM. We asked whether mtDNA packaging is more regulated than once thought. To address this, we analyzed DNase-seq experiments in 324 human cell types and found, for t...
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Published in | Genome research Vol. 28; no. 8; pp. 1158 - 1168 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Cold Spring Harbor Laboratory Press
01.08.2018
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Subjects | |
Online Access | Get full text |
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Summary: | Human mitochondrial DNA (mtDNA) is believed to lack chromatin and histones. Instead, it is coated solely by the transcription factor TFAM. We asked whether mtDNA packaging is more regulated than once thought. To address this, we analyzed DNase-seq experiments in 324 human cell types and found, for the first time, a pattern of 29 mtDNA Genomic footprinting (mt-DGF) sites shared by ∼90% of the samples. Their syntenic conservation in mouse DNase-seq experiments reflect selective constraints. Colocalization with known mtDNA regulatory elements, with G-quadruplex structures, in TFAM-poor sites (in HeLa cells) and with transcription pausing sites, suggest a functional regulatory role for such mt-DGFs. Altered mt-DGF pattern in interleukin 3-treated CD34
cells, certain tissue differences, and significant prevalence change in fetal versus nonfetal samples, offer first clues to their physiological importance. Taken together, human mtDNA has a conserved protein-DNA organization, which is likely involved in mtDNA regulation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1088-9051 1549-5469 |
DOI: | 10.1101/gr.230409.117 |