A5002148475- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer Genomics and Diagnostics
- Chromosomal and Genetic Variations
- Plant Molecular Biology Research
- Genomics and Phylogenetic Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Machine Learning in Bioinformatics
- Developmental Biology and Gene Regulation
- Pancreatic and Hepatic Oncology Research
- Pancreatic function and diabetes
- Animal Genetics and Reproduction
- Diabetes and associated disorders
- CRISPR and Genetic Engineering
- Bacterial Genetics and Biotechnology
- Genetic Syndromes and Imprinting
- Diabetes Management and Research
- Pluripotent Stem Cells Research
- Fungal and yeast genetics research
- Genetic factors in colorectal cancer
- NF-κB Signaling Pathways
- Bacteriophages and microbial interactions
Hebrew University of Jerusalem
2016-2025
Hadassah Medical Center
2022-2025
University of California, Berkeley
2011-2013
QB3
2010-2013
Hôpital Broca
2010
Hôpital Cochin
2010
Assistance Publique – Hôpitaux de Paris
2010
Université Paris Cité
2010
Délégation Paris 5
2010
Harvard University
2007
Abstract Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination tissue origins cfDNA, using a reference methylation atlas 25 human tissues and types. The method is validated silico simulations as well vitro mixes from different sources at known proportions. We show that plasma cfDNA healthy donors originates white blood cells (55%), erythrocyte progenitors (30%),...
Chromatin plays roles in processes governed by different time scales. To assay the dynamic behavior of chromatin living cells, we used genomic tiling arrays to measure histone H3 turnover G1-arrested Saccharomyces cerevisiae at single-nucleosome resolution over 4% genome, and lower (approximately 265 base pair) entire genome. We find that nucleosomes promoters are replaced more rapidly than coding regions replacement rates correlate with polymerase density. In addition, rapid is found known...
Covalent modification of histone proteins plays a role in virtually every process on eukaryotic DNA, from transcription to DNA repair. Many different residues can be covalently modified, and it has been suggested that these modifications occur great number independent, meaningful combinations. Published low-resolution microarray studies the combinatorial complexity patterns suffer confounding effects caused by averaging levels over multiple nucleosomes. To overcome this problem, we used...
We introduce the antibody landscape, a method for quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting antigenic variation among pathogen strains. generated landscapes study immune profiles covering 43 years influenza A/H3N2 virus evolution 69 individuals monitored infection over 6 and 225 pre- postvaccination. Upon vaccination, titers increased broadly, including previously encountered viruses far beyond extent cross-reactivity...
The Bacillus cereus group comprises the four valid species cereus, mycoides, thuringiensis and anthracis. Some isolates of B. are known to be psychrotolerant (growth at 7 °C or below). Here, specific sequence differences described between 16S rDNA, 23S 16S–23S rDNA spacer region genes major cold-shock protein homologue cspA in a variety mesophilic mycoides strains. Randomly amplified polymorphic DNA analysis using three different primers clearly separated strains both from rest group, as did...
The earliest stages of development in most metazoans are driven by maternally deposited proteins and mRNAs, with widespread transcriptional activation the zygotic genome occurring hours after fertilization, at a period known as maternal-to-zygotic transition (MZT). In Drosophila, MZT is preceded transcription small number genes that initiate sex determination, patterning, other early developmental processes; zinc-finger protein Zelda (ZLD) plays key role their activation. To better...
Abstract DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing window into cellular identity developmental processes 1 . Current datasets typically include only fraction of sites are often based either on cell lines underwent massive changes in culture or tissues containing unspecified mixtures cells 2–5 Here we describe human methylome atlas, deep whole-genome bisulfite sequencing, allowing fragment-level analysis across...
We describe the genome-wide distributions and temporal dynamics of nucleosomes post-translational histone modifications throughout maternal-to-zygotic transition in embryos Drosophila melanogaster. At mitotic cycle 8, when few zygotic genes are being transcribed, embryonic chromatin is a relatively simple state: there nucleosome free regions, undetectable levels methylation marks characteristic mature chromatin, low acetylation at small number loci. Histone increases by 12, but it not until...
The transition from a specified germ cell to population of pluripotent cells occurs rapidly following fertilization. During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila , DNA-binding protein Zelda (also known as Vielfaltig) required for transcriptional activation genome. Open associated with Zelda-bound loci, well more generally regions active transcription. Nonetheless, extent which...
Defining the transcriptome, repertoire of transcribed regions encoded in genome, is a challenging experimental task. Current approaches, relying on sequencing ESTs or cDNA libraries, are expensive and labor-intensive. Here, we present general approach for ab initio discovery complete transcriptome budding yeast, based only unannotated genome sequence millions short reads from single massively parallel run. Using novel algorithms, automatically construct highly accurate transcript catalog....
The availability of whole genome sequences and high-throughput genomic assays opens the door for in silico analysis transcription regulation. This includes methods discovering characterizing binding sites DNA-binding proteins, such as factors. A common representation factor is a position specific score matrix (PSSM). makes strong assumption that site positions are independent each other. In this work, we explore Bayesian network representations provide different tradeoffs between complexity...
Transcription factors that drive complex patterns of gene expression during animal development bind to thousands genomic regions, with quantitative differences in binding across bound regions mediating their activity. While we now have tools characterize the DNA affinities these proteins and precisely measure genome-wide distribution vivo, our understanding forces determine where, when, what extent they remains primitive. Here use a thermodynamic model transcription factor evaluate...
Proximity-ligation methods such as Hi-C allow us to map physical DNA-DNA interactions along the genome, and reveal its organization into topologically associating domains (TADs). As data accumulate, computational were developed for identifying domain borders in multiple cell types organisms. Here, we present PSYCHIC, a approach analyzing promoter-enhancer interactions. We use unified probabilistic model segment genome domains, which then merge hierarchically fit using local background model,...
Acetylation of histone H3 lysine 56 is a covalent modification best known as mark newly replicated chromatin, but it has also been linked to replication-independent replacement. Here, we measured H3K56ac levels at single-nucleosome resolution in asynchronously growing yeast cultures, well proceeding synchronously through the cell cycle. We developed quantitative model kinetics, which shows that largely explained by genomic replication timing and turnover rate each nucleosome, suggesting...
Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death organs affected by cancer be detected tissue-specific methylation patterns of circulating cell-free DNA (cfDNA). We elevated levels hepatocyte-derived cfDNA the plasma patients with liver metastases originating from different primary tumors, compared without metastases. In addition, localized pancreatic or colon showed hepatocyte cfDNA, suggesting inflicted...
Strenuous physical exercise causes a massive elevation in the concentration of circulating cell-free DNA (cfDNA), which correlates with effort intensity and duration. The cellular sources physiological drivers this phenomenon are unknown. Using methylation patterns cfDNA associated histones, we show that originates mostly extramedullary polymorphonuclear neutrophils. Strikingly, cardiomyocyte increases after marathon, consistent elevated troponin levels indicating low-level, delayed cardiac...
To better characterize how variation in regulatory sequences drives divergence gene expression, we undertook a systematic study of transcription factor binding and expression blastoderm embryos four species, which sample much the diversity 40 million-year old genus Drosophila: D. melanogaster, yakuba, pseudoobscura virilis. We compared measured by mRNA-seq, to genome-wide binding, ChIP-seq, factors involved early anterior-posterior patterning. found that mRNA levels are conserved than...
Significance TATA-binding protein (TBP)-associated factor 7l ( Taf7l ), Taf4b , and TBP-related 2 Trf2 ) were found to be three important atypical testis-specific core promoter recognition factors. However, whether there was any functional cross-talk between them at which stages of spermatogenesis remained uncharacterized. Here we report that − /Y becomes sterile rather than merely subfertile after backcrossing. Importantly, cooperates with but not late direct the transcription key...
Significance It is well-known that the risk of cancer varies widely between different tissues body with some cell types (e.g., colon, breast) being prone to cancer, whereas others brain, bone) only rarely develop tumors, but mechanism this phenomenon has not been elucidated. Recently, it was shown coefficient may actually be related inherent number stem-cell divisions go into generating each individual type during development. In work, we demonstrate highly correlated degree aberrant...
Highlights•Gata3, Eomes, Tfap2c, Myc, and Esrrb convert fibroblasts into iPSCs, iTSCs, iXENs•Esrrb, but not other pluripotency genes, can shift the TSC fate pluripotency•Esrrb induces by activation of a unique XEN-like state•The interplay between Eomes determines cell decisionSummaryFollowing fertilization, totipotent cells undergo asymmetric divisions, resulting in three distinct types late pre-implantation blastocyst: epiblast (Epi), primitive endoderm (PrE), trophectoderm (TE). Here, we...