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eukaryotic gene regulation

Ajinkya S Kawale, Lawrence F Povirk
Tyrosyl-DNA Phosphodiesterases 1 (TDP1) and 2 (TDP2) are eukaryotic enzymes that clean-up after aberrant topoisomerase activity. While TDP1 hydrolyzes phosphotyrosyl peptides emanating from trapped topoisomerase I (Top I) from the 3' DNA ends, topoisomerase 2 (Top II)-induced 5'-phosphotyrosyl residues are processed by TDP2. Even though the canonical functions of TDP1 and TDP2 are complementary, they exhibit little structural or sequence similarity. Homozygous mutations in genes encoding these enzymes lead to the development of severe neurodegenerative conditions due to the accumulation of transcription-dependent topoisomerase cleavage complexes underscoring the biological significance of these enzymes in the repair of topoisomerase-DNA lesions in the nervous system...
December 4, 2017: Nucleic Acids Research
Tobias Ahsendorf, Franz-Josef Müller, Ved Topkar, Jeremy Gunawardena, Roland Eils
The DNA microstates that regulate transcription include sequence-specific transcription factors (TFs), coregulatory complexes, nucleosomes, histone modifications, DNA methylation, and parts of the three-dimensional architecture of genomes, which could create an enormous combinatorial complexity across the genome. However, many proteins and epigenetic marks are known to colocalize, suggesting that the information content encoded in these marks can be compressed. It has so far proved difficult to understand this compression in a systematic and quantitative manner...
2017: PloS One
Judit Ámon, Rafael Fernández-Martín, Eszter Bokor, Antonietta Cultrone, Joan M Kelly, Michel Flipphi, Claudio Scazzocchio, Zsuzsanna Hamari
Nicotinate degradation has hitherto been elucidated only in bacteria. In the ascomycete Aspergillus nidulans, six loci, hxnS/AN9178 encoding the molybdenum cofactor-containing nicotinate hydroxylase, AN11197 encoding a Cys2/His2 zinc finger regulator HxnR, together with AN11196/hxnZ, AN11188/hxnY, AN11189/hxnP and AN9177/hxnT, are clustered and stringently co-induced by a nicotinate derivative and subject to nitrogen metabolite repression mediated by the GATA factor AreA. These genes are strictly co-regulated by HxnR...
December 2017: Open Biology
Alexandra Steffens, Marc Jakoby, Martin Hülskamp
Beige and Chediak Higashi (BEACH) domain-containing proteins (BDCPs) are facilitators of membrane-dependent cellular processes in eukaryotes. Mutations in BDCPs cause malfunctions of endosomal compartments in various cell types. Recently, the molecular analysis of the BDCP homolog gene SPIRRIG (SPI) has revealed a molecular function in P-bodies and the regulation of RNA stability. We therefore aimed to analyze, whether SPI has also a role in membrane-dependent processes. In this study, we show that SPI physically interacts with endosomal sorting complex required for transport associated ATPase Suppressor of K+-transport growth defect1 (SKD1) and its positive regulator, LYST Interacting Protein 5 (LIP5) and report genetic interactions between SPI and SKD1 and LIP5...
2017: Frontiers in Plant Science
Hany S Zinad, Inas Natasya, Andreas Werner
Non-coding RNAs are involved in epigenetic processes, playing a role in the regulation of gene expression at the transcriptional and post-transcriptional levels. A particular group of ncRNA are natural antisense transcripts (NATs); these are transcribed in the opposite direction to protein coding transcripts and are widespread in eukaryotes. Their abundance, evidence of phylogenetic conservation and an increasing number of well-characterized examples of antisense-mediated gene regulation are indicative of essential biological roles of NATs...
2017: Frontiers in Microbiology
Julie Soutourina
Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation...
December 6, 2017: Nature Reviews. Molecular Cell Biology
Olivier Godfroy, Toshiki Uji, Chikako Nagasato, Agnieszka P Lipinska, Delphine Scornet, Akira F Peters, Komlan Avia, Sebastien Colin, Mignerot Laure, Taizo Motomura, J Mark Cock, Susana M Coelho
Brown algae are one of the most developmentally complex groups within the eukaryotes. As in many land plants and animals, their main body axis is established early in development, when the initial cell gives rise to two daughter cells that have apical and basal identities, equivalent to shoot and root identities in land plants, respectively. We show here that mutations in the Ectocarpus DISTAG (DIS) gene lead to loss of basal structures during both the gametophyte and the sporophyte generations. Several abnormalities were observed in the germinating initial cell in dis mutants including increased cell size, disorganisation of the Golgi apparatus, disruption of the microtubule network and aberrant positioning of the nucleus...
December 5, 2017: Plant Cell
Guillermo Aquino-Jarquin
MicroRNAs (miRNA) are small, noncoding RNA molecules with a master role in the regulation of important tasks in different critical processes of cancer pathogenesis. Because there are different miRNAs implicated in all the stages of cancer, for example, functioning as oncogenes, this makes these small molecules suitable targets for cancer diagnosis and therapy. RNA-mediated interference has been one major approach for sequence-specific regulation of gene expression in eukaryotic organisms. Recently, the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system, first identified in bacteria and archaea as an adaptive immune response to invading genetic material, has been explored as a sequence-specific molecular tool for editing genomic sequences for basic research in life sciences and for therapeutic purposes...
December 5, 2017: Cancer Research
Pedro Robles, Víctor Quesada
Mitochondria are the powerhouse of eukaryotic cells because they are responsible for energy production through the aerobic respiration required for growth and development. These organelles harbour their own genomes and translational apparatus: mitochondrial ribosomes or mitoribosomes. Deficient mitochondrial translation would impair the activity of this organelle, and is expected to severely perturb different biological processes of eukaryotic organisms. In plants, mitoribosomes consist of three rRNA molecules, encoded by the mitochondrial genome, and an undefined set of ribosomal proteins (mitoRPs), encoded by nuclear and organelle genomes...
December 2, 2017: International Journal of Molecular Sciences
Clare Rogerson, Daniele Bergamaschi, Ryan Flo'shaughnessy
Eukaryotic nuclei are essential organelles, storing the majority of the cellular DNA, comprising the site of most DNA and RNA synthesis, controlling gene expression and therefore regulating cellular function. The majority of mammalian cells retain their nucleus throughout their lifetime, however, in three mammalian tissues the nucleus is entirely removed and its removal is essential for cell function. Lens fibre cells, erythroblasts and epidermal keratinocytes all lose their nucleus in the terminal differentiation pathways of these cell types...
December 5, 2017: Nucleus
Giada Rossignoli, Robert S Phillips, Alessandra Astegno, Marta Menegazzi, Carla Borri Voltattorni, Mariarita Bertoldi
Pyridoxal 5'-phosphate (PLP)-dependent enzymes catalyze a wide range of reactions of amino acids and amines, with the exception of glycogen phosphorylase which exhibits peculiar both substrate preference and chemical mechanism. They represent about 4% of the gene products in eukaryotic cells. Although structure-function investigations regarding these enzymes are copious, their regulation by post-translational modifications is largely unknown. Protein phosphorylation is the most common post-translational modification fundamental in mediating diverse cellular functions...
December 4, 2017: Amino Acids
Xin Xie, Piergiorgio Percipalle
In eukaryotic cells gene regulation is dependent on global genome organization. This is achieved, in response to favorable environmental conditions, through spatial redistribution of chromatin and changes in global epigenetic levels. This eventually drives movement of gene-rich chromatin loops and formation of DNA loops, consolidating neighborhoods of gene expression and silencing. One of the challenges for future work is to examine how these neighborhoods are formed and whether they host genes involved in the same cellular functions for sustained expression or silencing over time...
December 1, 2017: Biochemical and Biophysical Research Communications
Jian Chen, EnLi, Jinsheng Lai
Nucleosomes are the fundamental units of eukaryotic chromatin and can modulate the DNA accessibility for transcriptional regulatory elements. Many studies have demonstrated the effect of nucleosome organization on gene transcription level and transcriptional plasticity upon different conditions. Our recent study showed that nucleosome organization also plays an important role in modulating the plasticity of gene transcriptional status in maize. Here, we integrated our findings with previous studies on the role of nucleosome organization in regulation of gene transcription...
December 5, 2017: Nucleus
Paul V Attwood, Richmond Muimo
Nucleoside diphosphate kinases (NDPKs) are multifunctional proteins encoded by the nme (non-metastatic cells) genes, also called NM23. NDPKs catalyze the transfer of γ-phosphate from nucleoside triphosphates to nucleoside diphosphates by a ping-pong mechanism involving the formation of a high-energy phosphohistidine intermediate. Growing evidence shows that NDPKs, particularly NDPK-B, can additionally act as a protein histidine kinase. Protein kinases and phosphatases that regulate reversible O-phosphorylation of serine, threonine, and tyrosine residues have been studied extensively in many organisms...
December 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Kunnathur Murugesan Sakthivel, Venugopal Vinod Prabhu
Cancer originates from uncontrolled cell division in any part of the body. The universal burden of cancer continues to increase, and its treatment remains ever more challenging. Among several cancers, lung cancer is the second most common, causing 1.6 million deaths worldwide per year. Approximately 85% of lung cancers are non-small-cell lung carcinomas (NSCLCs), which are considerably more difficult to treat than other cancers. Although various imaging, biopsy, and histopathological analyses are widely used, there are no effective or reliable biomarkers for detecting early lung carcinoma, particularly NSCLC...
2017: Journal of Environmental Pathology, Toxicology and Oncology
Ahmed Mahas, C Neal Stewart, Magdy M Mahfouz
Genome editing has enabled broad advances and novel approaches in studies of gene function and structure; now, emerging methods aim to precisely engineer post-transcriptional processes. Developing precise, efficient molecular tools to alter the transcriptome holds great promise for biotechnology and synthetic biology applications. Different approaches have been employed for targeted degradation of RNA species in eukaryotes, but they lack programmability and versatility, thereby limiting their utility for diverse applications...
November 29, 2017: Biotechnology Advances
Nicolaas Hermans, Juriën Jori Huisman, Thomas Bauke Brouwer, Christopher Schächner, G Paul H van Heusden, Joachim Griesenbeck, John van Noort
The organization of DNA into chromatin is thought to regulate gene expression in eukaryotes. To study its structure in vitro, there is a need for techniques that can isolate specific chromosomal loci of natively assembled chromatin. Current purification methods often involve chemical cross-linking to preserve the chromatin composition. However, such cross-linking may affect the native structure. It also impedes single molecule force spectroscopy experiments, which have been instrumental to probe chromatin folding...
December 1, 2017: Scientific Reports
Weixi Liao, Bing Liu, Chih-Chun Chang, Ling-Jun Lin, Che Lin, Bor-Sen Chen, Zhen Xie
Insulators are non-coding gene regulatory elements in eukaryotic genome, which function as chromatin partitioning boundaries, and block interference across different chromatin domains. To facilitate modular construction of synthetic gene circuit that is usually composed of multiple transcription cassettes, unwanted cross-regulations between different cassettes should be avoided. Here, we developed a quantitative method to characterize the functional effect of three insulators on the cross-regulations of six promoters in mammalian cells...
December 1, 2017: ACS Synthetic Biology
Nicolas Personnic, Bianca Striednig, Hubert Hilbi
Legionella pneumophila is a water-borne opportunistic pathogen causing a life-threatening pneumonia called 'Legionnaires' disease'. The Legionella quorum sensing (Lqs) system produces and responds to the α-hydroxyketone signaling molecule 3-hydroxypentadecane-4-one (Legionella autoinducer-1, LAI-1). The Lqs system controls the switch between the replicative/non-virulent and the transmissive/virulent phase of L. pneumophila, and it is a major regulator of natural competence, motility and virulence of the pathogen...
November 27, 2017: Current Opinion in Microbiology
Joey Ward, Rona J Strawbridge, Mark E S Bailey, Nicholas Graham, Amy Ferguson, Donald M Lyall, Breda Cullen, Laura M Pidgeon, Jonathan Cavanagh, Daniel F Mackay, Jill P Pell, Michael O'Donovan, Valentina Escott-Price, Daniel J Smith
Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD)...
November 30, 2017: Translational Psychiatry
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