Alu repeats as transcriptional regulatory platforms in macrophage responses to M. tuberculosis infection
To understand the epigenetic regulation of transcriptional response of macrophages during early-stage M. tuberculosis (Mtb) infection, we performed ChIPseq analysis of H3K4 monomethylation (H3K4me1), a marker of poised or active enhancers. De novo H3K4me1 peaks in infected cells were associated with genes implicated in host defenses and apoptosis. Our analysis revealed that 40% of de novo regions contained human/primate-specific Alu transposable elements, enriched in the AluJ and S subtypes. These contained several transcription factor binding sites, including those for members of the MEF2 and ATF families, and LXR and RAR...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Bouttier, M., Laperriere, D., Memari, B., Mangiapane, J., Fiore, A., Mitchell, E., Verway, M., Behr, M. A., Sladek, R., Barreiro, L. B., Mader, S., White, J. H. Tags: Gene regulation, Chromatin and Epigenetics Source Type: research
Co-dependence between trypanosome nuclear lamina components in nuclear stability and control of gene expression
The nuclear lamina is a filamentous structure subtending the nuclear envelope and required for chromatin organization, transcriptional regulation and maintaining nuclear structure. The trypanosomatid coiled-coil NUP-1 protein is a lamina component functionally analogous to lamins, the major lamina proteins of metazoa. There is little evidence for shared ancestry, suggesting the presence of a distinct lamina system in trypanosomes. To find additional trypanosomatid lamina components we identified NUP-1 interacting proteins by affinity capture and mass-spectrometry. Multiple components of the nuclear pore complex (NPC) and a...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Maishman, L., Obado, S. O., Alsford, S., Bart, J.-M., Chen, W.-M., Ratushny, A. V., Navarro, M., Horn, D., Aitchison, J. D., Chait, B. T., Rout, M. P., Field, M. C. Tags: Gene regulation, Chromatin and Epigenetics Source Type: research
Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPAR{alpha}
Adaptation to fasting involves both Glucocorticoid Receptor (GRα) and Peroxisome Proliferator-Activated Receptor α (PPARα) activation. Given both receptors can physically interact we investigated the possibility of a genome-wide cross-talk between activated GR and PPARα, using ChIP- and RNA-seq in primary hepatocytes. Our data reveal extensive chromatin co-localization of both factors with cooperative induction of genes controlling lipid/glucose metabolism. Key GR/PPAR co-controlled genes switched from transcriptional antagonism to cooperativity when moving from short to prolonged hepatocyte fasting...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Ratman, D., Mylka, V., Bougarne, N., Pawlak, M., Caron, S., Hennuyer, N., Paumelle, R., De Cauwer, L., Thommis, J., Rider, M. H., Libert, C., Lievens, S., Tavernier, J., Staels, B., De Bosscher, K. Tags: Gene regulation, Chromatin and Epigenetics Source Type: research
Kinetics of transcription initiation directed by multiple cis-regulatory elements on the glnAp2 promoter
Transcription initiation is orchestrated by dynamic molecular interactions, with kinetic steps difficult to detect. Utilizing a hybrid method, we aim to unravel essential kinetic steps of transcriptional regulation on the glnAp2 promoter, whose regulatory region includes two enhancers (sites I and II) and three low-affinity sequences (sites III-V), to which the transcriptional activator NtrC binds. By structure reconstruction, we analyze all possible organization architectures of the transcription apparatus (TA). The main regulatory mode involves two NtrC hexamers: one at enhancer II transiently associates with site V such...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Wang, Y., Liu, F., Wang, W. Tags: Computational Biology Source Type: research
Editorial: NAR Awards 2016
(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 14, 2016 Category: Research Tags: Editorials Source Type: research
smiFISH and FISH-quant - a flexible single RNA detection approach with super-resolution capability
We present smiFISH (single molecule inexpensive FISH), an easy to use and flexible RNA visualization and quantification approach that uses unlabelled primary probes and a fluorescently labelled secondary detector oligonucleotide. The gene-specific probes are unlabelled and can therefore be synthesized at low cost, thus allowing to use more probes per mRNA resulting in a substantial increase in detection efficiency. smiFISH is also flexible since differently labelled secondary detector probes can be used with the same primary probes. We demonstrate that this flexibility allows multicolor labelling without the need to synthe...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Tsanov, N., Samacoits, A., Chouaib, R., Traboulsi, A.-M., Gostan, T., Weber, C., Zimmer, C., Zibara, K., Walter, T., Peter, M., Bertrand, E., Mueller, F. Tags: Recombination Methods Online Source Type: research
Personalized characterization of diseases using sample-specific networks
A complex disease generally results not from malfunction of individual molecules but from dysfunction of the relevant system or network, which dynamically changes with time and conditions. Thus, estimating a condition-specific network from a single sample is crucial to elucidating the molecular mechanisms of complex diseases at the system level. However, there is currently no effective way to construct such an individual-specific network by expression profiling of a single sample because of the requirement of multiple samples for computing correlations. We developed here with a statistical method, i.e. a sample-specific ne...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Liu, X., Wang, Y., Ji, H., Aihara, K., Chen, L. Tags: Computational Methods Methods Online Source Type: research
Order restricted inference for oscillatory systems for detecting rhythmic signals
Motivation: Many biological processes, such as cell cycle, circadian clock, menstrual cycles, are governed by oscillatory systems consisting of numerous components that exhibit rhythmic patterns over time. It is not always easy to identify such rhythmic components. For example, it is a challenging problem to identify circadian genes in a given tissue using time-course gene expression data. There is a great potential for misclassifying non-rhythmic as rhythmic genes and vice versa. This has been a problem of considerable interest in recent years. In this article we develop a constrained inference based methodology called Or...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Larriba, Y., Rueda, C., Fernandez, M. A., Peddada, S. D. Tags: Computational Methods Methods Online Source Type: research
Cell-based high-throughput compound screening reveals functional interaction between oncofetal HMGA2 and topoisomerase I
HMGA2 is an important chromatin factor that interacts with DNA via three AT-hook domains, thereby regulating chromatin architecture and transcription during embryonic and fetal development. The protein is absent from differentiated somatic cells, but aberrantly re-expressed in most aggressive human neoplasias where it is causally linked to cell transformation and metastasis. DNA-binding also enables HMGA2 to protect cancer cells from DNA-damaging agents. HMGA2 therefore is considered to be a prime drug target for many aggressive malignancies. Here, we have developed a broadly applicable cell-based reporter system which can...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Peter, S., Yu, H., Ivanyi-Nagy, R., Dröge, P. Tags: Protein-nucleic acid interaction, Targeted inhibition of gene function Methods Online Source Type: research
RNA2DNAlign: nucleotide resolution allele asymmetries through quantitative assessment of RNA and DNA paired sequencing data
We introduce RNA2DNAlign, a computational framework for quantitative assessment of allele counts across paired RNA and DNA sequencing datasets. RNA2DNAlign is based on quantitation of the relative abundance of variant and reference read counts, followed by binomial tests for genotype and allelic status at SNV positions between compatible sequences. RNA2DNAlign detects positions with differential allele distribution, suggesting asymmetries due to regulatory/structural events. Based on the type of asymmetry, RNA2DNAlign outlines positions likely to be implicated in RNA editing, allele-specific expression or loss, somati...
Source: Nucleic Acids Research - December 14, 2016 Category: Research Authors: Movassagh, M., Alomran, N., Mudvari, P., Dede, M., Dede, C., Kowsari, K., Restrepo, P., Cauley, E., Bahl, S., Li, M., Waterhouse, W., Tsaneva-Atanasova, K., Edwards, N., Horvath, A. Tags: Computational Methods, Genomics Methods Online Source Type: research
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(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 14, 2016 Category: Research Tags: Front-Matter/Back-Matter Source Type: research
Nucleic Acids Research: Editorial Board
(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 14, 2016 Category: Research Tags: Front-Matter/Back-Matter Source Type: research
Nucleic Acids Research: VOLUME 44 ISSUE 22 2016
(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 14, 2016 Category: Research Tags: Front-Matter/Back-Matter Source Type: research
A fast and powerful W-test for pairwise epistasis testing
(Source: Nucleic Acids Research)
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Wang, M. H., Sun, R., Guo, J., Weng, H., Lee, J., Hu, I., Sham, P. C., Zee, B. C.-Y. Tags: Corrigendum Source Type: research
Insightful directed evolution of Escherichia coli quorum sensing promoter region of the lsrACDBFG operon: a tool for synthetic biology systems and protein expression
Quorum sensing (QS) regulates many natural phenotypes (e.q. virulence, biofilm formation, antibiotic resistance), and its components, when incorporated into synthetic genetic circuits, enable user-directed phenotypes. We created a library of Escherichia coli lsr operon promoters using error-prone PCR (ePCR) and selected for promoters that provided E. coli with higher tetracycline resistance over the native promoter when placed upstream of the tet(C) gene. Among the fourteen clones identified, we found several mutations in the binding sites of QS repressor, LsrR. Using site-directed mutagenesis we restored all p-lsrR-box si...
Source: Nucleic Acids Research - December 1, 2016 Category: Research Authors: Hauk, P., Stephens, K., Mckay, R., Virgile, C. R., Ueda, H., Ostermeier, M., Ryu, K.-S., Sintim, H. O., Bentley, W. E. Tags: Synthetic Biology and Bioengineering Source Type: research
