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Published January 20, 2014 | Supplemental Material + Published
Journal Article Open

Evidence for Site-Specific Occupancy of the Mitochondrial Genome by Nuclear Transcription Factors


Mitochondria contain their own circular genome, with mitochondria-specific transcription and replication systems and corresponding regulatory proteins. All of these proteins are encoded in the nuclear genome and are post-translationally imported into mitochondria. In addition, several nuclear transcription factors have been reported to act in mitochondria, but there has been no comprehensive mapping of their occupancy patterns and it is not clear how many other factors may also be found in mitochondria. Here we address these questions by using ChIP-seq data from the ENCODE, mouseENCODE and modENCODE consortia for 151 human, 31 mouse and 35 C. elegans factors. We identified 8 human and 3 mouse transcription factors with strong localized enrichment over the mitochondrial genome that was usually associated with the corresponding recognition sequence motif. Notably, these sites of occupancy are often the sites with highest ChIP-seq signal intensity within both the nuclear and mitochondrial genomes and are thus best explained as true binding events to mitochondrial DNA, which exist in high copy number in each cell. We corroborated these findings by immunocytochemical staining evidence for mitochondrial localization. However, we were unable to find clear evidence for mitochondrial binding in ENCODE and other publicly available ChIP-seq data for most factors previously reported to localize there. As the first global analysis of nuclear transcription factors binding in mitochondria, this work opens the door to future studies that probe the functional significance of the phenomenon.

Additional Information

© 2014 Marinov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received August 20, 2013; Accepted November 18, 2013; Published January 20, 2014. Funding: This study has been supported by the Beckman Institute Functional Genomics Center, the Donald Bren Endowment, and NIH grants U54 HG004576, U54 HG006998, and GM062967. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Henry Amrhein, Diane Trout, Sean Upchurch and Sreeram Balasubramanian for technical and computational assistance. Author Contributions: Conceived and designed the experiments: GKM YEW BJW. Performed the experiments: GKM YEW. Analyzed the data: GKM YEW. Wrote the paper: GKM YEW DC BJW.

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Published - journal.pone.0084713.pdf

Supplemental Material - journal.pone.0084713.s001.pdf


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