A5102006630- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Machine Learning in Bioinformatics
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Viral-associated cancers and disorders
- Estrogen and related hormone effects
- Molecular Biology Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Bacterial Genetics and Biotechnology
- HIV Research and Treatment
- Invertebrate Immune Response Mechanisms
- Genomic variations and chromosomal abnormalities
- T-cell and B-cell Immunology
- Mosquito-borne diseases and control
- Genetic Mapping and Diversity in Plants and Animals
Florida State University
2014-2025
Massachusetts General Hospital
2005-2016
Harvard University
2005-2016
Tallahassee Orthopedic Clinic
2013
Fred Hutch Cancer Center
2012
Institut Curie
2010
University of Chicago
2010
Duke Medical Center
2010
Sorbonne Université
2010
Centre National de la Recherche Scientifique
2010
Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program. In mammals, replication timing is cell-type-specific with at least half genome switching during development, primarily units of 400-800 kilobases ('replication domains'), whose positions are preserved different cell types, conserved between species, and appear to confine long-range effects chromosome rearrangements. Early late correlate, respectively, open closed three-dimensional chromatin...
Abstract In breast cancer, overexpression of the small heat shock protein, HSP-27, is associated with increased anchorage-independent growth, invasiveness, and resistance to chemotherapeutic drugs poor prognosis reduced disease-free survival. Therefore, factors that increase expression HSP-27 in cancer are likely affect outcome treatment. this study, we show a strong correlation between elevated levels Brn-3b POU transcription factor high protein manipulated MCF-7 cells as well human...
Nucleosomes are the fundamental repeating unit of chromatin and comprise structural building blocks living eukaryotic genome. Micrococcal nuclease (MNase) has long been used to delineate nucleosomal organization. Microarray-based nucleosome mapping experiments in yeast have revealed regularly-spaced translational phasing nucleosomes. These data train computational models sequence-directed nuclesosome positioning, which identified ubiquitous strong intrinsic positioning signals. Here, we...
The eukaryotic genome is organized into nucleosomes, the fundamental units of chromatin. positions nucleosomes on DNA regulate protein-DNA interactions and in turn influence DNA-templated events. Despite increasing number genome-wide maps nucleosome position, how global changes gene expression relate to position poorly understood. We show that occupancy mapping experiments maize (Zea mays), particular genomic regions are highly susceptible variation introduced by differences extent which...
Among the currently available virus detection assays, those based on programmable CRISPR-Cas enzymes have advantage of rapid reporting and high sensitivity without requirement thermocyclers. Type III-A system is a multi-component multipronged immune effector, activated by viral RNA that previously has not been repurposed for disease owing in part to complex enzyme reconstitution process functionality. Here, we describe construction application method, an vivo-reconstituted system. This...
Several 400- to 800-kb murine chromosome domains switch from early late replication during loss of pluripotency, accompanied by a stable form gene silencing that is resistant reprogramming. We found that, whereas enhanced nuclease accessibility correlated with genome-wide, timing differentiation were exceptionally inaccessible even when early-replicating. Nonetheless, two studied in detail exhibited substantial changes transcriptional activity and higher-order chromatin unfolding confined...
Elucidating the transcriptional regulatory networks that underlie growth and development requires robust ways to define complete set of transcription factor (TF) binding sites. Although TF-binding sites are known be generally located within accessible chromatin regions (ACRs), pinpointing these DNA elements globally remains challenging. Current approaches primarily identify for a single TF (e.g. ChIP-seq), or detect ACRs but lack resolution consistently DNAse-seq, ATAC-seq). To address this...
Abstract Chromatin accessibility of a promoter is fundamental in regulating transcriptional activity. The histone variant H2A.Z has been shown to contribute this regulation, but its role remained poorly understood. Here, we prepare high-depth maps the position and H2A.Z-containing nucleosomes for all human Pol II promoters epithelial, mesenchymal isogenic cancer cell lines. We find that, contrast prevailing model, many different types active inactive structures are observed that differ their...
Genome-scale mapping of pre-replication complex proteins has not been reported in mammalian cells. Poor enrichment these at specific sites may be due to dispersed binding, poor epitope availability or cell cycle stage-specific binding. Here, we have mapped biotin-tagged ORC and MCM protein binding G1-synchronized populations Chinese hamster cells harboring amplified copies the dihydrofolate reductase (DHFR) locus, using avidin-affinity purification biotinylated chromatin followed by...
The unique chromatin signature of ES cells is fundamental to the pluripotency and differentiation cells. One key feature poised state master developmental genes that are transcriptionally repressed in but ready be activated response signals. Poised contains both H3 Lys-4 trimethylation (H3K4me3) Lys-27 (H3K27me3) methylation, indicating activating repressing potential. However, contribution non-covalent structure not well understood. To address whether remodeling nucleosomes important state,...
By selective attachment of a DNA cleavage agent to specific residues in the yeast TATA box binding protein (yTBP), we demonstrate that, solution, yTBP binds boxes both adenovirus major late promoter and CYC1 with only modest preference orientation well several overlapping sites. The general factors TFIIA TFIIB each increase rotational translational selectivity but are not sufficient, at least individually, confer unique polarity preinitiation complex. We conclude that TBP alone cannot define...
Histone variants are known to play a central role in genome regulation and maintenance. However, many inaccessible by antibody-based methods or bottom-up tandem mass spectrometry due their highly similar sequences. For many, the only tractable approach is with intact protein top-down spectrometry. Here, ultra-high-resolution FT-ICR MS MS/MS yield quantitative relative abundances of all detected HeLa H2A H2B isobaric isomeric label-free approach. We extend analysis identify relatively...
Significance Immunoglobulin and T-cell receptor genes are assembled in lymphoid cells from gene fragments by the process known as V(D)J recombination, which is initiated recombination activating (RAG)1/RAG2 recombinase. To ensure that occurs only correct cell type at right developmental stage, multiple layers of regulation necessary, including specific modifications chromatin. We show nucleosome positioning another important factor this regulation. Developmentally regulated changes help to...
Macrophages detect lipopolysaccharide (LPS) through toll-like receptor 4 (TLR-4) on the cell surface which initiates a signaling cascade resulting in recruitment of regulatory factors to chromatin and subsequent expression chemokine cytokine genes. Primary response genes, marked by poised promoters enhancers, are rapidly expressed after LPS stimulation, their gene products activate secondary genes via paracrine autocrine pathways. While cascades following macrophage activation well...
The monocyte to macrophage transition is marked by alterations both the structure and function of genome, including changes in histone post-translational modifications, DNA methylation, 3D nuclear architecture, expression lineage specific genes. nucleosome fundamental organizational unit eukaryotic genome underpins function. However, dynamics at promoters, which are essential for transcriptional regulation, understudied cellular differentiation. We conducted high-resolution chromatin...
SARS-CoV-2, the causative agent of COVID-19, is a positive-sense, single-stranded RNA virus that causes spectrum disease severity, from asymptomatic infection to severe illness long-term sequelae. Similar other human coronaviruses, SARS-CoV-2 proteins modulate host genomic responses through epigenomic modifications, facilitating viral replication and immune evasion. While nucleocapsid protein well known for its role in stability modulation, impact on chromatin organization remains unclear....
The eukaryotic nucleosome is the fundamental subunit of chromatin and plays functional roles in DNA templated processes, including replication transcription. In promoters, organization highly structured, with nucleosomes occupying canonical positions flanking transcription start site (TSS), thereby regulating access transcriptional machinery to underlying DNA. We determine whether this distribution present purple sea urchin, Strongylocentrotus purpuratus, a species ecological importance...
The fundamental building block of chromatin, the nucleosome, occupies 150 bp DNA in a spaced arrangement that is primary determinant regulation genome. nucleosomal organization some regions human genome has been described, but mapping these limited to few kilobases. We have explored two independent and complementary methods for high-throughput analysis mammalian chromatin structure. Through adaptations protocol used map yeast structure, we determined sites protection over large using tiling...
Nucleosome occupancy plays a key role in regulating access to eukaryotic genomes. Although various chromatin regulatory complexes are known regulate nucleosome occupancy, the of DNA sequence this regulation remains unclear, particularly mammals. To address problem, we measured distribution at high temporal resolution human cells hundreds genes during reactivation Kaposi's sarcoma-associated herpesvirus (KSHV). We show that redistribution peaks 24 h post-KSHV and nucleosomal redistributions...
Abstract The nucleosome is a fundamental structural and functional chromatin unit that affects nearly all DNA-templated events in eukaryotic genomes. It also biochemical substrate for higher order, cis-acting gene expression codes the monomeric packaging at multiple scales. To predict landscape of model plant genome, we used support vector machine computational algorithm trained on human to occupancy likelihood (NOL) across maize (Zea mays) genome. Experimentally validated NOL plots provide...
Altered chromatin structure is a hallmark of cancer, and inappropriate regulation may represent the origin transformation. Important studies have mapped human nucleosome distributions genome wide, but role in cancer progression has not been addressed. We developed MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map distribution at transcription start sites genome-wide primary lung colon adenocarcinoma tissue. Here, we confirm that redistribution an early, widespread...
The development and progression of lung adenocarcinoma, one the most common cancers, is driven by interplay genetic epigenetic changes role chromatin structure in malignant transformation remains poorly understood. We used systematic nucleosome distribution accessibility microarray mapping platforms to analyze genome-wide from normal tissues primary adenocarcinoma different grades stages. identified chromatin-based patterns across patients with cancer grade stage. Low-grade cancers had...
Drugs of abuse modify behavior by altering gene expression in the brain. Gene can be regulated changes DNA methylation as well histone modifications, which alter chromatin structure, compaction and accessibility. In order to better understand molecular mechanisms directing drug-induced we examined DNA-nucleosome interactions within promoter regions 858 genes human neuroblastoma cells (SH-SY5Y) exposed nicotine or cocaine. Widespread, drug- time-resolved repositioning nucleosomes was...
// Brittany S. Sexton 1,2 , Brooke R. Druliner 1,3 Daniel L. Vera 1,4 Denis Avey 1 Fanxiu Zhu and Jonathan H. Dennis 1,4,5 Department of Biological Science, The Florida State University, Tallahassee, FL, United States America 2 Current address: Massachusetts General Hospital Cancer Center Medicine, Harvard Medical School, Charlestown, MA, 3 Division Gastroenterology Hepatology, Mayo Clinic, Rochester, MN, 4 for Genomics Personalized Medicine 5 Institute Molecular Biophysics, Correspondence...