A5025034792- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Metabolomics and Mass Spectrometry Studies
- Zoonotic diseases and public health
- Metabolism and Genetic Disorders
- Bioinformatics and Genomic Networks
- Viral gastroenteritis research and epidemiology
- Bacillus and Francisella bacterial research
- Chromosomal and Genetic Variations
- HIV Research and Treatment
- Molecular Biology Techniques and Applications
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Genomics and Phylogenetic Studies
- Plant Virus Research Studies
- Peroxisome Proliferator-Activated Receptors
- Identification and Quantification in Food
- Autoimmune and Inflammatory Disorders Research
- DNA Repair Mechanisms
- ATP Synthase and ATPases Research
- Eosinophilic Esophagitis
Cornell University
2020-2024
New York State College of Veterinary Medicine
2022
Ben-Gurion University of the Negev
2014-2019
Abstract During meiotic prophase I, spermatocytes must balance transcriptional activation with homologous recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state. We explored the interplay between accessibility transcription through I of mammalian meiosis by measuring genome-wide patterns accessibility, nascent transcription, processed mRNA. find that Pol II is loaded on maintained in a paused state early during I. In later stages, released...
Compatibility between the nuclear (nDNA) and mitochondrial (mtDNA) genomes is important for organismal health. However, its significance major evolutionary processes such as speciation unclear, especially in vertebrates. We previously identified a sharp mtDNA-specific sequence divergence morphologically indistinguishable chameleon populations ( Chamaeleo chamaeleon recticrista ) across an ancient Israeli marine barrier (Jezreel Valley). Because mtDNA introgression gender-based dispersal were...
Oxidative phosphorylation (OXPHOS), a fundamental energy source in all human tissues, requires interactions between mitochondrial (mtDNA)- and nuclear (nDNA)-encoded protein subunits. Although such are to OXPHOS, bi-genomic coregulation is poorly understood. To address this question, we analyzed ∼8500 RNA-seq experiments from 48 body sites. Despite well-known variation activity, quantity, morphology, found overall positive mtDNA-nDNA OXPHOS genes’ co-expression across tissues. Nevertheless,...
Abstract How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we studied enhancer-promoter contact architecture and communication by integrating data from nucleosome-resolution maps, nascent transcription, perturbations to transcription-associated proteins thousands of candidate enhancers. Contact frequency between functionally validated pairs was most enriched near the +1 +2 nucleosomes at promoters, indicating that functional...
Abstract Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role in gene regulation, we do not understand evolutionary processes that led to emergence Pol or its transition rate-limiting actively controlled by transcription factors. Here analyzed species across tree life. Unicellular eukaryotes display slow acceleration near start sites transitioned longer-lived, focused pause metazoans. This event coincided with...
Abstract Introduction GWAS have identified multiple regions that confer risk for juvenile idiopathic arthritis (JIA). However, identifying the single nucleotide polymorphisms (SNPs) drive disease is impeded by SNPs’ identify loci being in linkage disequilibrium (LD) with hundreds of other SNPs. Since causal SNPs remain unknown, it difficult to target genes and use genetic information inform patient care. We used genotyping functional data primary human monocytes/macrophages nominate...
Abstract Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role in gene regulation, we do not understand evolutionary processes that led to emergence Pol or its transition rate-limiting actively controlled by transcription factors. Here analyzed species across tree life. We found unicellular eukaryotes display slow acceleration near start sites. This proto-paused-like state transitioned longer, focused pause derived...
Abstract Mitochondrial complex I (CI) is the largest multi-subunit oxidative phosphorylation (OXPHOS) protein complex. Recent availability of a high-resolution human CI structure, and from two non-human mammals, enabled predicting impact mutations on interactions involving each 44 subunits. However, experimentally assessing predicted requires an easy high-throughput method. Here, we created such platform by cloning all 37 nuclear DNA (nDNA) 7 mitochondrial (mtDNA)-encoded subunits into yeast...
Abstract The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a disease may have influenced evolution, we study changes in expression anthrax toxin receptor 2 ( ANTXR2 ), which encodes cell surface protein necessary for Bacillus anthracis virulence toxins cause disease. In immune cells, is 8-fold down-regulated all available samples compared non-human primates, indicating regulatory early the evolution modern humans. We also observe...
Quantification of isoform abundance has been extensively studied at the mature RNA level using RNA-seq but not precursor RNAs nascent sequencing.We address this problem with a new computational method called Deconvolution Expression for Nascent RNA-sequencing data (DENR), which models read-counts as mixture user-provided isoforms. The baseline algorithm is enhanced by machine-learning predictions active transcription start sites and an adjustment typical 'shape profile' along unit. We show...
E-protein transcription factors limit group 2 innate lymphoid cell (ILC2) development while promoting T differentiation from common progenitors. Inhibitors of DNA binding (ID) proteins block in progenitors to allow ILC2 development. However, whether E-proteins influence function upon maturity and activation remains unclear. Mice that overexpress ID1 under control the thymus-restricted proximal
Abstract During meiotic prophase I, germ cells must balance transcriptional activation with recombination and chromosome synapsis, biological processes requiring extensive changes to chromatin state structure. Here we explored the interplay between accessibility transcription across a detailed time-course of murine male meiosis by measuring genome-wide patterns accessibility, nascent transcription, processed mRNA. To understand relationship these parameters gene regulation recombination,...
Abstract Quantification of mature-RNA isoform abundance from RNA-seq data has been extensively studied, but much less attention devoted to quantifying the distinct precursor RNAs based on nascent RNA sequencing data. Here we address this problem with a new computational method called Deconvolution Expression for Nascent (DENR). DENR models read counts at each locus as mixture user-provided isoforms. The performance baseline algorithm is enhanced by use machine-learning predictions...
Abstract The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a disease influenced evolution, we studied changes in expression anthrax toxin receptor 2 ( ANTXR2 ), which encodes cell surface protein necessary for Bacillus anthracis virulence toxins cause disease. In immune cells, was 8-fold down-regulated all available samples compared non-human primates, indicating regulatory early the evolution modern humans. We also observed multiple...
Abstract In humans, oxidative phosphorylation (OXPHOS), the cellular energy producer, harbors ∼90 nuclear DNA (nDNA)- and mitochondrial (mtDNA)-encoded subunits. Although nDNA- mtDNA-encoded OXPHOS proteins physically interact, their transcriptional regulation profoundly diverges, thus questioning 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...
Mitochondrial complex I (C1) is the largest multi-subunit oxidative phosphorylation (OXPHOS) protein complex. Recent availability of a high-resolution human C1 structure, and from two non-human mammals, enabled predicting impact mutations on interactions involving each 44 subunits. However, experimentally assessing predicted requires an easy high-throughput method. Here, we created such platform by cloning all 37 nuclear DNA (nDNA) 7 mitochondrial (mtDNA)-encoded subunits into yeast...
Abstract How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we studied enhancer-promoter contact architecture and communication by integrating data from nucleosome-resolution maps, nascent transcription, perturbations to transcription-associated proteins thousands of candidate enhancers. Contact frequency between functionally validated pairs was most enriched near the +1 +2 nucleosomes at promoters, indicating that functional...