Biology subjects

Blumberg, A.

Publications and source records attributed to Blumberg, A..

2 recordsLinked to original sources

bioRxiv2017

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, 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.

genomics↗

bioRxiv2017

Oxidative-Phosphorylation Genes From The Mitochondrial And Nuclear Genomes Co-Express In All Human Tissues Except For The Ancient Brain

In humans, oxidative phosphorylation (OXPHOS), the cellular energy producer, harbors [~]90 nuclear DNA (nDNA)- and mitochondrial DNA (mtDNA)-encoded subunits. Although nDNA- and mtDNA-encoded OXPHOS proteins physically interact, their transcriptional regulation profoundly diverges, thus questioning their co-regulation. To address mtDNA-nDNA gene co-expression, we analyzed [~]8,500 RNA-seq Gene-Tissue-Expression (GTEx) experiments encompassing 48 human tissues. We found overall positive cross-tissue mtDNA-nDNA OXPHOS gene co-expression. Nevertheless, alternatively-spliced variants, as well as certain OXPHOS genes, did not converge into the main OXPHOS gene cluster, suggesting tissue-specific flavor of OXPHOS gene expression. Finally, unlike non-brain body sites, and neocortex and cerebellum ( mammalian brain), negative mito-nuclear expression correlation was found in the hypothalamus, basal ganglia and amygdala ( ancient brain). Analyses of co-expression, DNase-seq and ChIP-seq experiments identified candidate RNA-binding genes and CEBPb as best explaining this phenomenon. We suggest that evolutionary convergence of the mammalian brain into positive mtDNA-nDNA OXPHOS co-expression reflects adjustment to novel bioenergetics needs.

genomics↗