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Genetics and Genomics Commons

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Full-Text Articles in Genetics and Genomics

Genetic Signatures For Helicobacter Pylori Strains Of West African Origin, Kennady K. Bullock, Carrie L. Shaffer, Andrew W. Brooks, Ousman Secka, Mark H. Forsyth, Mark S. Mcclain, Timothy L. Cover Nov 2017

Genetic Signatures For Helicobacter Pylori Strains Of West African Origin, Kennady K. Bullock, Carrie L. Shaffer, Andrew W. Brooks, Ousman Secka, Mark H. Forsyth, Mark S. Mcclain, Timothy L. Cover

Veterinary Science Faculty Publications

Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of …


Transcriptome-Wide Identification Of The Rna-Binding Landscape Of The Chromatin-Associated Protein Parp1 Reveals Functions In Rna Biogenesis, Manana Melikishvili, Julia H. Chariker, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf Nov 2017

Transcriptome-Wide Identification Of The Rna-Binding Landscape Of The Chromatin-Associated Protein Parp1 Reveals Functions In Rna Biogenesis, Manana Melikishvili, Julia H. Chariker, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Recent studies implicate Poly (ADP-ribose) polymerase 1 (PARP1) in alternative splicing regulation, and PARP1 may be an RNA-binding protein. However, detailed knowledge of RNA targets and the RNA-binding region for PARP1 are unknown. Here we report the first global study of PARP1–RNA interactions using PAR–CLIP in HeLa cells. We identified a largely overlapping set of 22 142 PARP1–RNA-binding peaks mapping to mRNAs, with 20 484 sites located in intronic regions. PARP1 preferentially bound RNA containing GC-rich sequences. Using a Bayesian model, we determined positional effects of PARP1 on regulated exon-skipping events: PARP1 binding upstream and downstream of the skipped exons …


Mutsβ Abundance And Msh3 Atp Hydrolysis Activity Are Important Drivers Of Ctg•Cag Repeat Expansions, Norma Keogh, Kara Y. Chan, Guo-Min Li, Robert S. Lahue Sep 2017

Mutsβ Abundance And Msh3 Atp Hydrolysis Activity Are Important Drivers Of Ctg•Cag Repeat Expansions, Norma Keogh, Kara Y. Chan, Guo-Min Li, Robert S. Lahue

Toxicology and Cancer Biology Faculty Publications

CTG•CAG repeat expansions cause at least twelve inherited neurological diseases. Expansions require the presence, not the absence, of the mismatch repair protein MutSβ (Msh2-Msh3 heterodimer). To evaluate properties of MutSβ that drive expansions, previous studies have tested under-expression, ATPase function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems. Additionally, some variants destabilize MutSβ, potentially masking the effects of biochemical alterations of the variations. Here, human Msh3 was mutated to selectively inactivate MutSβ. Msh3−/− cells are severely defective for CTG•CAG repeat expansions but show full activity on contractions. Msh3−/− cells provide a single, isogenic system …


Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried Jul 2017

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ωave. We found …


The Foxo Transcription Factor Controls Insect Growth And Development By Regulating Juvenile Hormone Degradation In The Silkworm, Bombyx Mori, Baosheng Zeng, Yuping Huang, Jun Xu, Takahiro Shiotsuki, Hua Bai, Subba Reddy Palli, Yongping Huang, Anjiang Tan May 2017

The Foxo Transcription Factor Controls Insect Growth And Development By Regulating Juvenile Hormone Degradation In The Silkworm, Bombyx Mori, Baosheng Zeng, Yuping Huang, Jun Xu, Takahiro Shiotsuki, Hua Bai, Subba Reddy Palli, Yongping Huang, Anjiang Tan

Entomology Faculty Publications

Forkhead box O (FOXO) functions as the terminal transcription factor of the insulin signaling pathway and regulates multiple physiological processes in many organisms, including lifespan in insects. However, how FOXO interacts with hormone signaling to modulate insect growth and development is largely unknown. Here, using the transgene-based CRISPR/Cas9 system, we generated and characterized mutants of the silkworm Bombyx mori FOXO (BmFOXO) to elucidate its physiological functions during development of this lepidopteran insect. The BmFOXO mutant (FOXO-M) exhibited growth delays from the first larval stage and showed precocious metamorphosis, pupating at the end of the fourth instar (trimolter) rather …


Microarray Dataset Of Transient And Permanent Dna Methylation Changes In Hela Cells Undergoing Inorganic Arsenic-Mediated Epithelial-To-Mesenchymal Transition, Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf May 2017

Microarray Dataset Of Transient And Permanent Dna Methylation Changes In Hela Cells Undergoing Inorganic Arsenic-Mediated Epithelial-To-Mesenchymal Transition, Meredith Eckstein, Matthew Rea, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

The novel dataset presented here represents the results of the changing pattern of DNA methylation profiles in HeLa cells exposed to chronic low dose (0.5 µM) sodium arsenite, resulting in epithelial-to-mesenchymal transition, as well as DNA methylation patterns in cells where inorganic arsenic has been removed. Inorganic arsenic is a known carcinogen, though not mutagenic. Several mechanisms have been proposed as to how inorganic arsenic drives carcinogenesis such as regulation of the cell׳s redox potential and/or epigenetics. In fact, there are gene specific studies and limited genome-wide studies that have implicated epigenetic factors such as DNA methylation in inorganic arsenic-mediated …


Epigenomic Reprogramming In Inorganic Arsenic-Mediated Gene Expression Patterns During Carcinogenesis, Meredith Eckstein, Rebekah Eleazer, Matthew Rea, Yvonne N. Fondufe-Mittendorf Mar 2017

Epigenomic Reprogramming In Inorganic Arsenic-Mediated Gene Expression Patterns During Carcinogenesis, Meredith Eckstein, Rebekah Eleazer, Matthew Rea, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Arsenic is a ubiquitous metalloid that is not mutagenic but is carcinogenic. The mechanism(s) by which arsenic causes cancer remain unknown. To date, several mechanisms have been proposed, including the arsenic-induced generation of reactive oxygen species (ROS). However, it is also becoming evident that inorganic arsenic (iAs) may exert its carcinogenic effects by changing the epigenome, and thereby modifying chromatin structure and dynamics. These epigenetic changes alter the accessibility of gene regulatory factors to DNA, resulting in specific changes in gene expression both at the levels of transcription initiation and gene splicing. In this review, we discuss recent literature reports …


Genome-Wide Dna Methylation Reprogramming In Response To Inorganic Arsenic Links Inhibition Of Ctcf Binding, Dnmt Expression And Cellular Transformation, Matthew Rea, Meredith Eckstein, Rebekah Eleazer, Caroline Smith, Yvonne N. Fondufe-Mittendorf Feb 2017

Genome-Wide Dna Methylation Reprogramming In Response To Inorganic Arsenic Links Inhibition Of Ctcf Binding, Dnmt Expression And Cellular Transformation, Matthew Rea, Meredith Eckstein, Rebekah Eleazer, Caroline Smith, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. …


Inhibition Of Mammalian Glycoprotein Ykl-40 Identification Of The Physiological Ligand, Abhishek A. Kognole, Christina M. Payne Jan 2017

Inhibition Of Mammalian Glycoprotein Ykl-40 Identification Of The Physiological Ligand, Abhishek A. Kognole, Christina M. Payne

Chemical and Materials Engineering Faculty Publications

YKL-40 is a mammalian glycoprotein associated with progression, severity, and prognosis of chronic inflammatory diseases and a multitude of cancers. Despite this well documented association, identification of the lectin′s physiological ligand and, accordingly, biological function has proven experimentally difficult. YKL-40 has been shown to bind chito-oligosaccharides; however, the production of chitin by the human body has not yet been documented. Possible alternative ligands include proteoglycans, polysaccharides, and fibers like collagen, all of which makeup the extracellular matrix. It is likely that YKL-40 is interacting with these alternative polysaccharides or proteins within the body, extending its function to cell biological roles …