iScience (Feb 2019)

mtDNA Chromatin-like Organization Is Gradually Established during Mammalian Embryogenesis

  • Shani Marom,
  • Amit Blumberg,
  • Anshul Kundaje,
  • Dan Mishmar

Journal volume & issue
Vol. 12
pp. 141 – 151

Abstract

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Summary: Unlike the nuclear genome, the mammalian mitochondrial genome (mtDNA) is thought to be coated solely by mitochondrial transcription factor A (TFAM), whose binding sequence preferences are debated. Therefore, higher-order mtDNA organization is considered much less regulated than both the bacterial nucleoid and the nuclear chromatin. However, our recently identified conserved DNase footprinting pattern in human mtDNA, which co-localizes with regulatory elements and responds to physiological conditions, likely reflects a structured higher-order mtDNA organization. We hypothesized that this pattern emerges during embryogenesis. To test this hypothesis, we analyzed assay for transposase-accessible chromatin sequencing (ATAC-seq) results collected during the course of mouse and human early embryogenesis. Our results reveal, for the first time, a gradual and dynamic emergence of the adult mtDNA footprinting pattern during embryogenesis of both mammals. Taken together, our findings suggest that the structured adult chromatin-like mtDNA organization is gradually formed during mammalian embryogenesis. : Biological Sciences; Developmental Genetics; Molecular Genetics; Developmental Biology Subject Areas: Biological Sciences, Developmental Genetics, Molecular Genetics, Developmental Biology