A5037951351- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Genomic variations and chromosomal abnormalities
- Pediatric health and respiratory diseases
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Chromosomal and Genetic Variations
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- RNA modifications and cancer
- RNA Research and Splicing
- Acute Lymphoblastic Leukemia research
- NF-κB Signaling Pathways
- Cancer-related molecular mechanisms research
- Service-Learning and Community Engagement
- Telomeres, Telomerase, and Senescence
- Coastal wetland ecosystem dynamics
- Virus-based gene therapy research
- Cancer Genomics and Diagnostics
- Biomedical and Engineering Education
- Coral and Marine Ecosystems Studies
New College of Florida
2014-2024
Florida State University
2008-2014
Tallahassee Orthopedic Clinic
2012
Fred Hutch Cancer Center
2012
The laboratory mouse shares the majority of its protein-coding genes with humans, making it premier model organism in biomedical research, yet two mammals differ significant ways. To gain greater insights into both shared and species-specific transcriptional cellular regulatory programs mouse, Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications replication domains throughout genome diverse cell tissue types. By...
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...
To identify evolutionarily conserved features of replication timing and their relationship to epigenetic properties, we profiled genome-wide in four human embryonic stem cell (hESC) lines, hESC-derived neural precursor cells (NPCs), lymphoblastoid cells, two induced pluripotent lines (hiPSCs), compared them with related mouse types. Results confirm the conservation coordinately replicated megabase-sized “replication domains” punctuated by origin-suppressed regions. Differentiation-induced...
DNA replication in mammals is regulated via the coordinate firing of clusters replicons that duplicate megabase-sized chromosome segments at specific times during S-phase. Cytogenetic studies show these "replicon clusters" coalesce as subchromosomal units persist through multiple cell generations, but molecular boundaries such have remained elusive. Moreover, extent to which changes timing occur differentiation and their relationship transcription has not been rigorously investigated. We...
Differentiation of mouse embryonic stem cells (mESCs) is accompanied by changes in replication timing. To explore the relationship between timing and cell fate transitions, we constructed genome-wide replication-timing profiles 22 independent lines representing 10 stages early development, transcription for seven these stages. Replication were cell-type specific, with 45% genome exhibiting significant at some point during development that generally coordinated transcription. Comparison late...
We have investigated the role of histone methyltransferase G9a in establishment silent nuclear compartments. Following conditional knockout mouse ESCs, 167 genes were significantly up-regulated, and no strongly down-regulated. A partially overlapping set 119 up-regulated after differentiation G9a-depleted cells to neural precursors. Promoters these G9a-repressed AT rich H3K9me2 enriched but H3K4me3 depleted not highly DNA methylated. Representative found be close periphery, which was for...
Abnormal replication timing has been observed in cancer but no study comprehensively evaluated this misregulation. We generated genome-wide replication-timing profiles for pediatric leukemias from 17 patients and three cell lines, as well normal B T cells. Nonleukemic EBV-transformed lymphoblastoid lines displayed highly stable that were more similar to cells than leukemias. Leukemias each other considerably heterogeneous nonleukemic controls. Some differences patient specific, while others...
Many types of epigenetic profiling have been used to classify stem cells, stages cellular differentiation, and cancer subtypes. Existing methods focus on local chromatin features such as DNA methylation histone modifications that require extensive analysis for genome-wide coverage. Replication timing has emerged a highly stable cell type-specific feature is regulated at the megabase-level easily comprehensively analyzed genome-wide. Here, we describe classification method using 67 individual...
Abstract Background Eukaryotic DNA replication is regulated at the level of large chromosomal domains (0.5–5 megabases in mammals) within which replicons are activated relatively synchronously. These replicate a specific temporal order during S-phase and our genome-wide analyses timing have demonstrated that this domain stable property cell types. Results We developed ReplicationDomain http://www.replicationdomain.org as web-based database for analysis maps (replication profiles) from...
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...
In multicellular organisms, developmental changes to replication timing occur in 400–800 kb domains across half the genome. While examples of epigenetic control have been described, a role for DNA sequence mammalian replication-timing regulation has not substantiated. To assess sequences directing timing, we profiled mice carrying genetically rearranged Human Chromosome 21 (Hsa21). two distinct mouse cell types, Hsa21 maintained human-specific except at points rearrangement. Changes...
Cellular differentiation and reprogramming are accompanied by changes in replication timing 3D organization of large-scale (400 to 800 Kb) chromosomal domains ('replication domains'), but few gene products have been identified whose disruption affects these properties.Here we show that deletion esBAF chromatin-remodeling complex components BAF250a Brg1, not BAF53a, disrupts at specific domains. Also, BAF250a-deficient fibroblasts reprogrammed a pluripotency-like state failed reprogram many...
Facioscapulohumeral muscular dystrophy (FSHD) is linked to contraction of an array tandem 3.3-kb repeats (D4Z4) at 4q35.2 from 11-100 copies 1-10 copies. The extent which D4Z4 affects overall chromatin organization remains unclear. Because DNA replication timing highly predictive long-range interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts four patients three individuals each other a...
We recently identified a set of chromosome domains that are early replicating uniquely in pluripotent cells. Their switch from to late replication occurs just prior germ layer commitment, associated with stable form gene silencing is difficult reverse. Here, we discuss results demonstrating these among the least sensitive regions genome global digestion by either MNase or restriction enzymes. This inaccessible chromatin state persists whether their physically distended compact configuration,...
We constructed high‐resolution replication timing profiles in mouse and human embryonic stem cells (mESCs hESCs) before after differentiation to multiple lineages. demonstrate that domains of coordinate ("replication domains") delineate distinct units chromosomes with cell‐type specific boundaries. During differentiation, smaller discordantly replicating consolidate into larger coordinately replicated units. Moreover, induced pluripotent (iPS) re‐acquire the ESCs. When mESCs were followed...
Aging is affected by genetic and environmental factors, cigarette smoking strongly associated with accumulation of senescent cells. In this study, we wanted to identify genes that may potentially be beneficial for cell survival in response smoke thereby contribute development cellular senescence.Primary human bronchial epithelial cells from five healthy donors were cultured, treated or without 1.5% extract (CSE) 24 h passaged into replicative senescence. Transcriptome changes monitored using...
Algae in the dinoflagellate family Symbiodiniaceae are endocellular photosymbionts of corals and other cnidarians. This close relationship is disrupted when seawater temperature increases, causing coral bleaching eventually affecting entire reefs. Although between animal host photosymbiont has been well-studied, little known about bacterial community associated with culture. We compared microbial communities three isolates from different species genus Symbiodinium (formerly as clade A)...
Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in contexts development and disease. methylation by methyltransferases (Dnmts) downstream chromatin reorganization transcriptional changes are thought to impact replication, yet this remains be comprehensively tested. Using cell-based genome-wide approaches measure timing, we identified a number genomic regions undergoing subtle but reproducible timing various Dnmt-mutant mouse embryonic stem...