A5001736863- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Circadian rhythm and melatonin
- Viral Infectious Diseases and Gene Expression in Insects
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
- Protein Structure and Dynamics
- Fungal and yeast genetics research
- CRISPR and Genetic Engineering
- RNA regulation and disease
- DNA and Nucleic Acid Chemistry
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Genetics and Biotechnology
- Animal Genetics and Reproduction
- Molecular Biology Techniques and Applications
- Pluripotent Stem Cells Research
- Genetics, Bioinformatics, and Biomedical Research
The University of Texas Southwestern Medical Center
2016-2025
Southwestern Medical Center
2010-2024
Walter Reed National Military Medical Center
2020-2021
American Chemical Society
2010
Baylor University Medical Center
2007
Emory University
2005
Southern Methodist University
2005
Howard Hughes Medical Institute
1989-2004
National Institutes of Health
1977-2004
National Institute of Allergy and Infectious Diseases
2004
A 30-amino-acid segment of C/EBP, a newly discovered enhancer binding protein, shares notable sequence similarity with the cellular Myc transforming protein. Display these respective amino acid sequences on an idealized α helix revealed periodic repetition leucine residues at every seventh position over distance covering eight helical turns. The array least four leucines was also noted in Fos and Jun proteins, as well that yeast gene regulatory GCN4. polypeptide segments containing arrays...
Mammalian cells respond to changes in oxygen availability through a conserved pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha subunit of HIF targeted for degradation under normoxic conditions ubiquitin-ligase complex recognizes hydroxylated proline residue HIF. We identified family prolyl hydoxylase (HPH) enzymes appear be responsible this posttranslational modification. In cultured mammalian cells, inappropriate accumulation caused forced expression HIF-1alpha was...
In an effort to identify protein factors that play a regulatory role in the differentiation of adipocytes, we have isolated two genes encode polypeptides related CCAAT/enhancer-binding (C/EBP; hereafter termed C/EBP alpha). The proteins encoded by these C/EBP-related genes, beta and delta, exhibit similar DNA-binding specificities affinities compared with alpha. Furthermore, delta readily form heterodimers one another as well transcriptional activating capacity newly identified isoforms was...
Transcriptional control signals of a model eukaryotic protein-coding gene have been identified by new procedure in vitro mutagenesis. This method allows small clusters nucleotide residues to be substituted site-directed manner without causing the addition or deletion other sequences. Transcription assays systematic series these clustered point mutants led identification three distinct located within 105-nucleotide immediately upstream from where transcription begins.
Here we describe the cloning and characterization of a PAS domain transcription factor termed endothelial PAS-1 (EPAS1). This protein shares 48% sequence identity with hypoxia inducible (HIF-1alpha) lesser similarity other members basic helix-loop-helix/PAS family factors. Like HIF-1alpha, EPAS1 binds to activates from DNA element originally isolated erythropoietin gene containing 5'-GCCCTACGTGCTGTCTCA-3'. Activation by both HIF-1alpha is stimulated hypoxic conditions. forms heterodimeric...
Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle. Although built to fluctuate at or near 24-hour cycle, clock can be entrained by light, activity, food. Here we show DNA-binding activity heterodimers is regulated redox state nicotinamide adenine dinucleotide (NAD) cofactors in purified system. The reduced forms cofactors, NAD(H) NADP(H), strongly enhance DNA binding heterodimers, whereas oxidized inhibit....
In two previous studies we described the properties of a heat-stable DNA-binding protein present in rat liver nuclei. This protein, hereafter termed C/EBP, is capable selective binding to CCAAT homology several viral promoters (Graves et al. 1986), as well core common many enhancers (Johnson 1987). We now report isolation recombinant clone gene that encodes C/EBP. Expression bacterial cells yields binds vitro both and enhancer homology, providing conclusive evidence single product accounts...
Terminal differentiation of cultured 3T3-L1 fibroblasts to the adipogenic phenotype is potently stimulated by dexamethasone (DEX) and methylisobutylxanthine (MIX). Previous studies have shown that these hormones induce expression genes encoding two members CCAAT/enhancer binding protein (C/EBP) family transcription factors. In absence new synthesis DEX activates gene C/EBP delta. Likewise, MIX a direct inducer beta expression. Optimal conditions for entail 2-day period wherein confluent are...
Budding yeast grown under continuous, nutrient-limited conditions exhibit robust, highly periodic cycles in the form of respiratory bursts. Microarray studies reveal that over half genome is expressed periodically during these metabolic cycles. Genes encoding proteins having a common function similar temporal expression patterns, and genes specifying functions associated with energy metabolism tend to be exceptionally robust periodicity. Essential cellular events occur synchrony cycle,...
Interleukin-4 (IL-4) is an immunomodulatory cytokine secreted by activated T lymphocytes, basophils, and mast cells. It plays important role in modulating the balance of helper (Th) cell subsets, favoring expansion Th2 lineage relative to Th1. Imbalance these lymphocyte subsets has been implicated immunological diseases including allergy, inflammation, autoimmune disease. IL-4 may mediate its biological effects, at least part, activating a tyrosine-phosphorylated DNA binding protein. This...
Mature virions of herpes simplex virus type 1 contain an activating factor that primes transcription from the five virally encoded immediate early (IE) genes. This activator is specified by a 65-kD polypeptide termed VP16. The action VP16 mediated through cis-regulatory elements located in regions adjacent to each IE gene. Although normally introduced into cells infecting virions, its trans-activating function can also be observed cotransfecting with plasmid encodes along reporter gene...
C/EBP is a rat liver nuclear protein capable of sequence-specific interaction with DNA. The DNA sequences to which binds in vitro have been implicated the control messenger RNA synthesis. It has therefore predicted that will play role regulating gene expression mammalian cells. region polypeptide required for direct identified and shown bear amino acid sequence relatedness product myc, fos, jun proto-oncogenes. arrangement these related led prediction new structural motif, termed "leucine...
Mice lacking the hypoxia-inducible transcription factor EPAS1 die at mid-gestation. Despite normal morphological development of circulatory system, EPAS1-deficient mice display pronounced bradycardia. In addition to vascular endothelium, is expressed intensively in organ Zuckerkandl (OZ), principle source catecholamine production mammalian embryos. embryos contained substantially reduced levels. Mid-gestational lethality was rescued by administration precursor DOPS pregnant females. We...
This paper presents the results of experiments that determine chromosomal location mouse gene encoding CCAAT/enhancer binding protein (C/EBP) and measure its expression as a function tissue type temporal period development in mice rats. Three alleles C/EBP were identified according to restriction fragment length polymorphisms. The strain distribution pattern three was determined recombinant inbred strains compared other genes. These mapped position within 2.5 centimorgans (cM) structural...
This report describes the identification and purification of a nuclear protein from rat liver that binds selectively to DNA sequences associated with several animal virus enhancers. The binding activity was tracked by direct DNase I footprinting through four steps biochemical fractionation. These procedures led polypeptide species exhibiting an apparent molecular weight 20 kD accounts for enhancer activity. dimethyl sulfate assays were used examine manner in which purified elements SV40,...
Many RNA regulatory proteins controlling pre-messenger splicing contain serine:arginine (SR) repeats. Here, we found that these SR domains bound hydrogel droplets composed of fibrous polymers the low-complexity domain heterogeneous ribonucleoprotein A2 (hnRNPA2). Hydrogel binding was reversed upon phosphorylation by CDC2-like kinases 1 and 2 (CLK1/2). Mutated variants changing serine to glycine (SR-to-GR variants) also hnRNPA2 hydrogels but were not affected CLK1/2. When expressed in...