TY - JOUR
T1 - A common pattern of DNase I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization
AU - Blumberg, Amit
AU - Danko, Charles G.
AU - Kundaje, Anshul
AU - Mishmar, Dan
N1 - Publisher Copyright:
© 2018 Blumberg et al.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85050859009&partnerID=8YFLogxK
U2 - 10.1101/gr.230409.117
DO - 10.1101/gr.230409.117
M3 - Article
C2 - 30002158
AN - SCOPUS:85050859009
SN - 1088-9051
VL - 28
SP - 1158
EP - 1168
JO - Genome Research
JF - Genome Research
IS - 8
ER -