A5086553158- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Connective tissue disorders research
- interferon and immune responses
- Genomic variations and chromosomal abnormalities
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- Pluripotent Stem Cells Research
- Bone Metabolism and Diseases
- Viral Infections and Immunology Research
- Craniofacial Disorders and Treatments
- Ubiquitin and proteasome pathways
- Genomics and Phylogenetic Studies
- Plant Molecular Biology Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2016-2025
National Institutes of Health
2016-2025
Haldia Institute of Technology
2022-2024
University of Maryland, College Park
2009-2015
Genomic structural variation is an important and abundant source of genetic phenotypic variation. Here, we describe the first systematic genome-wide analysis copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), fluorescent situ (FISH). The CGH panel included 90 animals from 11 Bos taurus , three indicus composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions...
The Krüppel-associated box zinc finger protein (KRAB-ZFP) family diversified in mammals. majority of human KRAB-ZFPs bind transposable elements (TEs), however, since most TEs are inactive humans it is unclear whether emerged to suppress TEs. We demonstrate that many recently murine also TEs, including the active ETn, IAP, and L1 families. Using a CRISPR/Cas9-based engineering approach, we genetically deleted five large clusters target de-repressed, unleashing TE-encoded enhancers. Homozygous...
In recent years, advances in bioinformatics approaches have allowed a systematic characterization of circular RNAs (circRNAs) across variety cell types. Demonstration type specificity, regulated expression, and conservation between species all suggest that circRNAs functional importance. Especially, investigators begun focusing on the possibility operate as part competing endogenous RNA (ceRNA) regulatory networks are proposed to play critical roles normal development pathologic conditions...
Fate-determining transcription factors (TFs) can promote lineage-restricted transcriptional programs from common progenitor states. The inner cell mass (ICM) of mouse blastocysts co-expresses the TFs NANOG and GATA6, which drive bifurcation ICM into either epiblast (Epi) or primitive endoderm (PrE), respectively. Here, we induce GATA6 in embryonic stem cells-that also express NANOG-to characterize how a state co-expression opposing resolves divergent lineages. Surprisingly, find that co-bind...
The ventricular zone (VZ) of the nervous system contains radial glia cells that were originally considered relatively homogenous in their gene expression, but a detailed characterization transcriptional diversity these VZ has not been reported. Here, we performed single-cell RNA sequencing to characterize heterogeneity neural progenitors within and subventricular (SVZ) ganglionic eminences (GEs), source all forebrain GABAergic neurons. By using transgenic mouse line enrich for cells,...
Abstract The terminal differentiation of osteoblasts and subsequent formation bone marks an important phase in palate development that leads to the separation oral nasal cavities. While morphogenetic events preceding palatal osteogenesis are well explored, major gaps remain our understanding molecular mechanisms driving this bony union fusing palate. Through bulk, single-nucleus, spatially resolved RNA-sequencing analyses developing secondary palate, we identify a shift transcriptional...
Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG organized into multiprotein complexes that recruited to DNA via cis-acting elements known as "Polycomb response elements" (PREs). In Drosophila, PREs consist binding sites different DNA-binding proteins, some and others unknown. Identification these is crucial understanding mechanism recruitment PREs. We report here identification Combgap (Cg), a...
Immature T cells undergo a process of positive selection in the thymus when their new cell receptor (TCR) engages and signals response to self-peptides. As matures, slew negative regulatory molecules, including inhibitory surface glycoprotein CD5, are up-regulated proportion strength self-peptide signal. Together these regulators dampen TCR-proximal signaling help avoid any subsequent peripheral activation by Paradoxically, antigen-specific initially expressing more CD5 (CD5hi) have been...
Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Information on physiological roles and underlying mechanisms particular linkages during human development are limited. Here, relying genomic constraint scores, we identify 10 patients multiple congenital anomalies caused by hemizygous variants in OTUD5, encoding a K48/K63 deubiquitylase. By studying these mutations, find that OTUD5 controls neuroectodermal differentiation...
Abstract A comprehensive characterization of epigenomic organization in the embryonic mouse forebrain will enhance our understanding neurodevelopment and provide insight into mechanisms neurological disease. Here we collected single-cell chromatin accessibility profiles from four distinct neurogenic regions using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands differentially accessible peaks, many restricted to progenitor cell types or brain regions. integrated snATAC-Seq...
Polycomb group response elements (PREs) in Drosophila are DNA-elements that recruit proteins (PcG) to chromatin and regulate gene expression. PREs easily recognizable the genome as strong peaks of PcG-protein binding over discrete DNA fragments; many small but statistically significant PcG also observed domains. Surprisingly, vivo deletion four characterized from regulated invected-engrailed (inv-en) complex did not disrupt formation H3K27me3 domain affect inv-en expression embryos or larvae...
Melorheostosis is a rare sclerosing dysostosis characterized by asymmetric exuberant bone formation. Recently, we reported that somatic mosaicism for MAP2K1-activating mutations causes radiographical “dripping candle wax” melorheostosis. We now report SMAD3 in lesions of four unrelated patients with endosteal pattern In vitro, the stimulated TGF-β pathway osteoblasts, enhanced nuclear translocation and target gene expression, inhibited proliferation. Osteoblast differentiation mineralization...
Beef is one of the leading sources protein, B vitamins, iron, and zinc in human food. palatability based on three general criteria: tenderness, juiciness, flavor, which tenderness thought to be most important factor. In this study, we found that beef measured by Warner-Bratzler shear force (WBSF), was dramatically increased acute stress. Microarray analysis qPCR identified a variety genes were differentially expressed. Pathway showed these involved immune response regulation metabolism...
Abstract Breeding of genetically resistant chickens to Marek’s disease (MD) is a vital strategy poultry health. To find the markers underlying genetic resistance MD, copy number variation (CNV) was examined in inbred MD-resistant and -susceptible chicken lines. A total 45 CNVs were found four lines chickens, 28 potentially involved immune response cell proliferation, etc. Importantly, two related with MD transmitted descendent recombinant congenic that differ susceptibility MD. Our findings...
Abstract Background Marek's disease (MD) is a lymphoproliferative in chickens caused by virus (MDV) and characterized T cell lymphoma infiltration of lymphoid cells into various organs such as liver, spleen, peripheral nerves muscle. Resistance to MD risk have long been thought be influenced both genetic environmental factors, the combination which contributes observed outcome an individual. We hypothesize that after MDV infection, genes related MD-resistance or -susceptibility may exhibit...
Imprinted genes occur in discrete clusters that are coordinately regulated by shared DNA elements called Imprinting Control Regions. H19 and Igf2 linked imprinted play critical roles development. Loss of imprinting (LOI) at the IGF2/H19 locus on maternal chromosome is associated with developmental disorder Beckwith Wiedemann Syndrome (BWS) several cancers. Here we use comprehensive genetic genomic analyses to follow muscle development a mouse model BWS dissect separate for misexpression...
KRAB-zinc finger proteins (KZFPs) comprise the largest family of mammalian transcription factors, rapidly evolving within and between species. Most KZFPs repress endogenous retroviruses (ERVs) other retrotransposons, with KZFP gene numbers correlating ERV load across species, suggesting coevolution. How new emerge in response to invasions is currently unknown. Using a combination long-read sequencing technologies genome assembly, we present first detailed comparative analysis young clusters...
Type VII osteogenesis imperfecta (OI), caused by recessive CRTAP mutations, is predominantly lethal in the first year of life. Due to its early lethality, little known about bone dysplasia mechanism. RNA-seq analysis differentiated osteoblasts siblings with a non-lethal homozygous CRTAP-null variant showed an enrichment gene ontology terms involved DNA replication and cell cycle compared control. BrdU incorporation confirmed ≈2-fold increase proliferation proband comparison control cells. In...
Abstract We investigated Transglutaminase 2 (TGM2) in high fat diet (HFD) obese mice, finding upregulated TGM2+ adipose tissue macrophages (ATMs) HFD epididymal white (eWAT) compared to chow (CD) eWAT. Using Tgm2 CRISPR silencing, we examined TGM2 modulation of inflammation vitro within bone marrow-derived (BMMs), as well co-cultured eWAT stromal vascular fraction (SVF) cells. silencing BMMs led increased pro-inflammation, control. In contrast, exposure SVF recombinant anti-inflammatory...
Marek's disease (MD) is a lymphoproliferative in chicken induced by virus (MDV). Although studies have focused on the genetic differences between resistant and susceptible chicken, less known about role of epigenetic factors MD. In this study, genome-wide histone modifications non-MHC-associated lines were examined. We found that tri-methylation at H3 Lys4 (H3K4me3) enrichment positively correlated with expression protein coding genes as well microRNA (miRNA) genes, whereas Lys27 (H3K27me3)...
Abstract Background Marek’s disease (MD) is a neoplastic in chickens caused by the MD virus (MDV). Successful vaccine development against has resulted increased virulence of MDV and understanding genetic resistance to is, therefore, crucial long-term control strategies. Also, epigenetic factors are believed be one major determinants response. Results Here, we carried out comprehensive analyses landscape induced MDV, utilizing genome-wide histone H3 lysine 4 27 trimethylation maps from...
Marek's disease (MD) is a highly contagious, lymphomatous of chickens induced by herpesvirus, virus (MDV) that the cause major annual losses to poultry industry. MD pathogenesis involves multiple stages including an early cytolytic phase and latency, transitions between these are governed several host environmental factors. The success vaccination strategies has led increased virulence MDV selective breeding naturally resistant seen as viable alternative. While gene expression studies have...
Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical, physiological properties. However, the molecular mechanisms regulating their maturation remain poorly understood. Here, via single-cell transcriptomics, we show that obligate NMDA-type glutamate receptor (NMDAR) subunit gene Grin1 mediates transcriptional regulation of expression in specific subtypes...