A5024558337- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Gene expression and cancer classification
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Genomic variations and chromosomal abnormalities
- Plant responses to water stress
- DNA and Nucleic Acid Chemistry
- Fungal and yeast genetics research
- Mitochondrial Function and Pathology
- Neurobiology and Insect Physiology Research
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Evolution and Genetic Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Carcinogens and Genotoxicity Assessment
- Advanced Proteomics Techniques and Applications
Duke University Hospital
2014-2025
Duke Medical Center
2015-2025
Duke University
2012-2021
Massachusetts Institute of Technology
2001-2007
Howard Hughes Medical Institute
2002-2007
Brigham and Women's Hospital
2005
The University of Texas Southwestern Medical Center
1998-2000
Texas A&M University
1994-1997
From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation still needed characterize how used help produce functional organism (see Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for Caenorhabditis elegans genome, and The modENCODE Consortium 1787 Drosophila melanogaster full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites,...
Despite the successes of genomics, little is known about how genetic information produces complex organisms. A look at crucial functional elements fly and worm genomes could change that. The National Human Genome Research Institute's modENCODE project (the model organism ENCyclopedia Of DNA Elements) was set up in 2007 with goal identifying all sequence-based two important experimental organisms, Caenorhabditis elegans Drosophila melanogaster. Armed data, geneticists will be able to...
The covalent modification of nucleosomal histones has emerged as a major determinant chromatin structure and gene activity. To understand the interplay between various histone modifications, including acetylation methylation, we performed genome-wide analysis in higher eukaryote. We found binary pattern modifications among euchromatic genes, with active genes being hyperacetylated for H3 H4 hypermethylated at Lys 4 79 H3, inactive hypomethylated deacetylated same residues. Furthermore,...
A large collection of new modENCODE and ENCODE genome-wide chromatin data sets from cell lines developmental stages in worm, fly human are analysed; this reveals many conserved features organization among the three organisms, as well notable differences composition locations repressive chromatin. This study describes numerous Homo sapiens, Drosophila melanogaster Caenorhabditis elegans generated by consortia. The results point to while identifying Genome function is dynamically regulated...
The origin recognition complex (ORC) specifies replication location. Saccharomyces cerevisiae ORC recognizes the ARS (autonomously replicating sequence) consensus sequence (ACS), but only a subset of potential genomic sites are bound, suggesting other chromosomal features influence binding. Using high-throughput sequencing to map binding and nucleosome positioning, we show that yeast origins characterized by an asymmetric pattern positioned nucleosomes flanking ACS. sequences sufficient...
We have combined standard micrococcal nuclease (MNase) digestion of nuclei with a modified protocol for constructing paired-end DNA sequencing libraries to map both nucleosomes and subnucleosome-sized particles at single base-pair resolution throughout the budding yeast genome. found that partially unwrapped can occupy same position within cell population, suggesting dynamic behavior. By varying time MNase digestion, we been able observe changes reflect differential sensitivity particles,...
The mechanisms by which metazoan origins of DNA replication are defined, regulated, and influenced chromosomal events remain poorly understood. To gain insights into these mechanisms, we developed a systematic approach using Drosophila high-resolution genomic microarray to determine timing, identify origins, map protein-binding sites along chromosome arm. We defined temporal pattern that correlates with the density active transcription. These data indicate influence transcription status on...
The origin recognition complex (ORC) is an essential DNA replication initiation factor conserved in all eukaryotes. In Saccharomyces cerevisiae, ORC binds to specific elements; however, higher eukaryotes, exhibits little sequence specificity vitro or vivo. We investigated the genome-wide distribution of Drosophila and found that localizes chromosomal locations absence any discernible simple motif. Although no clear motif emerged, we were able use machine learning approaches accurately...
In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this in the bacterium Bacillus subtilis slows elongation, we proposed effect contributes to evolutionary pressure selecting transcription-replication bias. This selection might have been based purely on for speedy replication; alternatively, slowed actually represent an average...
DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic epigenetic inheritance. Considerable progress has been made toward understanding how chromatin modifications regulate program; in contrast, we know relatively little about role landscape defining are selected regulated. Here, describe program context for multiple cell lines using data generated by...
Extensive departures from balanced gene dose in aneuploids are highly deleterious. However, we know very little about the relationship between copy number and expression aneuploid cells. We determined transcript abundance (expression) genome-wide Drosophila S2 cells by DNA-Seq RNA-Seq. found that for >43 Mb of genome, primarily range one to five copies, show a male genotype (∼ two X chromosomes four sets autosomes, or 2X;4A). Both autosomes showed dosage compensation. chromosome was elevated...
Mutational heterogeneity must be taken into account when reconstructing evolutionary histories, calibrating molecular clocks, and predicting links between genes disease. Selective pressures various DNA transactions have been invoked to explain the heterogeneous distribution of genetic variation species, within populations, in tissue-specific tumors. To examine relationships such variations leading- lagging-strand replication fidelity mismatch repair, we accumulated 40,000 spontaneous...
Abstract Background Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at organismal level, but common immortalized cell lines and tumors, where they may be an advantage cells. In order explore biological consequences changes Drosophila genome, we resequenced genomes 19 tissue-culture generated RNA-Seq profiles. Results Our work revealed dramatic duplications deletions all lines. We found three evidence indicating that were...
Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2–7 helicase loading to form prereplicative (pre-RC). Although pre-RC assembly is well characterized in vitro, process poorly understood within local chromatin environment surrounding origins. To reveal how architecture modulates selection and activation, we “footprinted” nucleosomes, transcription factors, proteins at multiple points during Saccharomyces cerevisiae cell cycle. Our...
Myb–MuvB (MMB)/dREAM is a nine-subunit complex first described in Drosophila as repressor of transcription, dependent on E2F2 and the RBFs. Myb, an integral member MMB, curiously plays no role silencing test genes previously analyzed. Moreover, Myb activating DNA replication egg chamber follicle cells. The essential functions for are executed part MMB. This duality function lead to hypothesis that which contains both known activator proteins, might switching mechanism sites developmental...
Precise DNA replication is crucial for genome maintenance, yet this process has been inherently difficult to study on a genome-wide level in untransformed differentiated metazoan cells. To determine how can be repressed, we examined regions selectively under-replicated Drosophila polytene salivary glands, and found they are transcriptionally silent enriched the repressive H3K27me3 mark. In first analysis of binding origin recognition complex (ORC) tissue, find that ORC dramatically reduced...
DNA replication is a dynamic process that occurs in temporal order along each of the chromosomes. A consequence temporally coordinated activation origins establishment broad domains (>100 kb) replicate either early or late S phase. This partitioning genome into and important for maintaining stability, gene dosage, epigenetic inheritance; however, molecular mechanisms define establish these are poorly understood. The modENCODE Project provided an opportunity to investigate chromatin features...