A5033719708- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cytomegalovirus and herpesvirus research
- RNA regulation and disease
- Herpesvirus Infections and Treatments
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Pediatric Urology and Nephrology Studies
- Genomics and Rare Diseases
- Renal and related cancers
- Cancer-related Molecular Pathways
- MicroRNA in disease regulation
- Aquatic Ecosystems and Phytoplankton Dynamics
- Fish Biology and Ecology Studies
- Plant Molecular Biology Research
- Cancer-related gene regulation
- Salmonella and Campylobacter epidemiology
- Physiological and biochemical adaptations
- Immune Response and Inflammation
- Prenatal Screening and Diagnostics
- Birth, Development, and Health
- Protist diversity and phylogeny
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
University of Iowa
2012-2022
Iowa City Public Library
2021
Van Andel Institute
2011
Abstract Renal agenesis is a devastating birth defect, and although genes encoding retinoic acid signaling components have been shown to be important for renal... (RA) one of the more extreme examples congenital anomalies kidney urinary tract (CAKUT). Bilateral renal almost invariably fatal at birth, unilateral can lead future health issues including end-stage disease. Genetic investigations identified several gene variants that cause RA, EYA1, LHX1, WT1. However, whereas compound null...
Abstract The effects of rapid acute depletion components RNA polymerase II (Pol II) general transcription factors (GTFs) that are thought to be critical for formation preinitiation complexes (PICs) and initiation in vitro were quantified HAP1 cells using precision nuclear run-on sequencing (PRO-Seq). average dependencies each factor across >70 000 promoters varied widely even though levels depletions similar. Some the could attributed presence or absence core promoter elements such as...
We report the development of OikoBase (http://oikoarrays.biology.uiowa.edu/Oiko/), a tiling array-based genome browser resource for Oikopleura dioica, metazoan belonging to urochordates, closest extant group vertebrates. facilitates retrieval and mining variety useful genomics information. First, it includes which interrogates 1260 genomic sequence scaffolds features gene, transcript CDS annotation tracks. Second, we annotated gene models with ontology (GO) terms InterPro domains are...
Abstract To better understand human RNA polymerase II (Pol II) promoters in the context of promoter-proximal pausing and local chromatin organization, 5′ 3′ ends nascent capped transcripts locations nearby nucleosomes were accurately identified through sequencing at exceptional depth. High-quality visualization tools revealed a preferred sequence that defines over 177 000 core with strengths varying by >10 000-fold. This signature encompasses binding site for TFIID is surprisingly...
Predator-induced defences are a prominent example of phenotypic plasticity found from single-celled organisms to vertebrates. The water flea Daphnia pulex is very convenient ecological genomic model for studying predator-induced as it exhibits substantial morphological changes under predation risk. Most importantly, however, genetically identical clones can be transcriptionally profiled both control and risk conditions compared due the availability sequenced reference genome. Earlier gene...
The large genome of human cytomegalovirus (HCMV) is transcribed by RNA polymerase II (Pol II). However, it not known how closely this betaherpesvirus follows host transcriptional paradigms. We applied PRO-Seq and PRO-Cap methods to profile quantify transcription initiation productive elongation across the virus genomes in late infection. A major similarity between viral that treatment cells with P-TEFb inhibitor flavopiridol preempts virtually all elongation, which otherwise covers most HCMV...
Abstract Interactions of the RNA polymerase II (Pol II) preinitiation complex (PIC) and paused early elongation complexes with first downstream (+1) nucleosome are thought to be functionally important. However, current methods limited for investigating these relationships, both cellular chromatin human cytomegalovirus (HCMV) genome. Digestion DNA fragmentation factor (DFF) before immunoprecipitation (DFF-ChIP) precisely revealed similarities major differences in PICs driven by TBP on host...
How human cytomegalovirus (HCMV) infection impacts the transcription of host genome remains incompletely understood. Here, we examine global consequences primary foreskin fibroblasts (HFFs) on by RNA polymerase I, II, and III over course a lytic using PRO-Seq. The expected rapid induction innate immune response genes is observed with specific subsets exhibiting dissimilar expression kinetics. We find minimal effects Pol II initiation, but increased rates release paused into productive...
HCMV infects more than half of the world population and persists lifelong in its hosts. Although generally asymptomatic, infection can lead to life-threating disease immunosuppressed individuals.
Beta- and gammaherpesviruses late transcription factors (LTFs) target viral promoters containing a TATT sequence to drive after DNA replication has begun. Human cytomegalovirus (HCMV), betaherpesvirus, uses the UL87 LTF bind both host RNA polymerase II (Pol II), whereas UL79 been suggested productive elongation. Here we apply integrated functional genomics (dTag system, PRO-Seq, ChIP-Seq, promoter function assays) uncover contribution of diversity in sequences determining degree scope which...
Abstract Background Salmonella enterica serovar Typhi ( S . Typhi) is a human-specific pathogen that causes typhoid fever, and remains global health problem especially in developing countries. Its pathogenesis complex host response poorly understood. In Africa, fever can be major cause of morbidity young infected children. The onset the illness insidious clinical diagnosis often unreliable. Gold standard blood culture diagnostic services are limited, thus rapid, sensitive, affordable test...
Approximately half of purified mammalian RNA polymerase II (Pol II) is associated with a tightly interacting sub-stoichiometric subunit, Gdown1. Previous studies have established that Gdown1 inhibits transcription initiation through competitive interactions general factors and blocks the Pol termination activity factor 2 (TTF2). However, biological functions remain poorly understood. Here, we utilized genetic, microscopic, multi-omics approaches to functionally characterize in three human...
Proper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein interacts with transcription factors chromatin remodeling complexes, required embryonic formation of cerebral cortex. Here we show Akirin2 plays a mechanistically distinct role in maintaining healthy neurons during cortical maturation. Restricting loss to excitatory resulted progressive neurodegeneration via necroptosis...
The 22q11.2 deletion syndrome (22q11.2DS) is the most common contiguous microdeletion affecting humans and exhibits extreme phenotypic heterogeneity. Patients can manifest any combination of comorbidities including congenital heart disease, hypoparathyroidism, cleft palate, kidney abnormalities, neurodevelopmental disorders, immune dysfunction. Immunodeficiency present in majority patients with 22q11.2DS second leading cause death these patients. Knowing genetic determinants dysfunction will...
Abstract The interpretation of clinical chromosomal microarrays (CMAs) has historically relied on the relevance identified copy number variants (CNVs) to phenotype. New guidelines are focused standardizing pathogenicity classifications based genomic location, gene content, and previous publications, rather than immediate relevance. Here we report DISCRIMINATOR, which was developed assign provisional location by integrating information putative benign pathogenic loci in human genome. However,...
Abstract While copy number variants (CNVs) have been identified as an important cause of rare genetic disorders, they also in unaffected control populations, making clinical interpretation these lesions challenging. Discriminating benign CNVs from those pathogenic for therefore, relies on understanding what regions the human genome are tolerant to variation. Benign-Ex is a python-based program that uses information databases generate one or more interval map(s) and then identifies optimal...
Abstract Interactions of the RNA polymerase II (Pol II) preinitiation complex (PIC) and paused early elongation complexes with first downstream (+1) nucleosome are thought to be functionally important. However, current methods limited for investigating these relationships, both cellular chromatin human cytomegalovirus (HCMV) genome. Digestion DNA fragmentation factor (DFF) before immunoprecipitation (DFF-ChIP) precisely revealed similarities major differences in PICs driven by TBP on host...
Mutation of the c-Myb proto-oncogene causes leukemias and lymphomas in birds mammals. Vertebrates contain three representatives Myb gene family consisting A-, B- c-Myb, all which encode DNA-binding factors that bind to promoter regions are important for proper expression target genes. In flies, have a single gene, Dm-Myb is required epigenetic maintenance ON state genes subsequent their activation, plays key role regulation mitotic phase Here, we identify additional targets, nearly...
We used paired-end next generation sequencing (NGS) to characterize the classic isoform-specific
Summary Proper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein interacts with transcription factors chromatin remodeling complexes, required embryonic formation of cerebral cortex. Here we show Akirin2 plays a mechanistically distinct role in maintaining healthy neurons during cortical maturation. Restricting loss to excitatory resulted progressive neurodegeneration via...