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https://www.readbyqxmd.com/read/28240320/analysis-of-co-associated-transcription-factors-via-ordered-adjacency-differences-on-motif-distribution
#1
Gaofeng Pan, Jijun Tang, Fei Guo
Transcription factors (TFs) binding to specific DNA sequences or motifs, are elementary to the regulation of transcription. The gene is regulated by a combination of TFs in close proximity. Analysis of co-TFs is an important problem in understanding the mechanism of transcriptional regulation. Recently, ChIP-seq in mapping TF provides a large amount of experimental data to analyze co-TFs. Several studies show that if two TFs are co-associated, the relative distance between TFs exhibits a peak-like distribution...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28235418/baalchip-bayesian-analysis-of-allele-specific-transcription-factor-binding-in-cancer-genomes
#2
Ines de Santiago, Wei Liu, Ke Yuan, Martin O'Reilly, Chandra Sekhar Reddy Chilamakuri, Bruce A J Ponder, Kerstin B Meyer, Florian Markowetz
Allele-specific measurements of transcription factor binding from ChIP-seq data are key to dissecting the allelic effects of non-coding variants and their contribution to phenotypic diversity. However, most methods of detecting an allelic imbalance assume diploid genomes. This assumption severely limits their applicability to cancer samples with frequent DNA copy-number changes. Here we present a Bayesian statistical approach called BaalChIP to correct for the effect of background allele frequency on the observed ChIP-seq read counts...
February 24, 2017: Genome Biology
https://www.readbyqxmd.com/read/28224496/computationally-tractable-multivariate-hmm-in-genome-wide-mapping-studies
#3
Hyungwon Choi, Debashis Ghosh, Zhaohui Qin
Hidden Markov model (HMM) is widely used for modeling spatially correlated genomic data (series data). In genomics, datasets of this kind are generated from genome-wide mapping studies through high-throughput methods such as chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq). When multiple regulatory protein binding sites or related epigenetic modifications are mapped simultaneously, the correlation between data series can be incorporated into the latent variable inference in a multivariate form of HMM, potentially increasing the statistical power of signal detection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28224494/modelling-chip-seq-data-using-hmms
#4
Veronica Vinciotti
Chromatin ImmunoPrecipitation-sequencing (ChIP-seq) experiments have now become routine in biology for the detection of protein binding sites. In this chapter, we show how hidden Markov models can be used for the analysis of data generated by ChIP-seq experiments. We show how a hidden Markov model can naturally account for spatial dependencies in the ChIP-seq data, how it can be used in the presence of data from multiple ChIP-seq experiments under the same biological condition, and how it naturally accounts for the different IP efficiencies of individual ChIP-seq experiments...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28223367/coordination-of-myeloid-differentiation-with-reduced-cell-cycle-progression-by-pu-1-induction-of-micrornas-targeting-cell-cycle-regulators-and-lipid-anabolism
#5
Lauren A Solomon, Shreya Podder, Jessica He, Nicholas L Jackson Chornenki, Kristen Gibson, Rachel G Ziliotto, Jess Rhee, Rodney P DeKoter
During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26-transformation specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28219948/genomic-integration-of-wnt-%C3%AE-catenin-and-bmp-smad1-signaling-coordinates-foregut-and-hindgut-transcriptional-program
#6
Mariana L Stevens, Praneet Chaturvedi, Scott A Rankin, Melissa Macdonald, Sajjeev Jagannathan, Masashi Yukawa, Artem Barski, Aaron M Zorn
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28215080/a-scalable-epitope-tagging-approach-for-high-throughput-chip-seq-analysis
#7
Xiong Xiong, Yanxiao Zhang, Jian Yan, Surbhi Jain, Sora Chee, Bing Ren, Huimin Zhao
Eukaryotic transcriptional factors (TFs) typically recognize short genomic sequences alone or together with other proteins to modulate gene expression. Mapping of TF-DNA interactions in the genome is crucial for understanding the gene regulatory programs in cells. While chromatin immunoprecipitation followed by sequencing (ChIP-Seq) is commonly used for this purpose, its application is severely limited by the availability of suitable antibodies for TFs. To overcome this limitation, we developed an efficient and scalable strategy named cmChIP-Seq that combines the clustered regularly interspaced short palindromic repeats (CRISPRs) technology with microhomology mediated end joining (MMEJ) to genetically engineer a TF with an epitope tag...
February 19, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28213474/a-bayesian-approach-for-analysis-of-whole-genome-bisulphite-sequencing-data-identifies-disease-associated-changes-in-dna-methylation
#8
Owen J L Rackham, Sarah R Langley, Thomas Oates, Eleni Vradi, Nathan Harmston, Prashant K Srivastava, Jacques Behmoaras, Petros Dellaportas, Leonardo Bottolo, Enrico Petretto
DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate...
February 17, 2017: Genetics
https://www.readbyqxmd.com/read/28213272/rev-erb-regulation-of-cholesterologenesis
#9
Sadichha Sitaula, Jinsong Zhang, Fernanda Ruiz, Thomas P Burris
REV-ERBα and REV-ERBβ are heme regulated nuclear receptors that are known to regulate metabolic pathways. We previously demonstrated that treatment of mice with synthetic REV-ERB agonists suppressed plasma cholesterol levels and the hepatic levels of the rate limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-Mmethylglutaryl-CoA reductase). Here, we characterize the role of REV-ERB on the cholesterol biosynthetic pathway in greater detail. The REV-ERB agonist SR9009 reduced plasma cholesterol levels in both wild type C57Bl/6 and low density lipoprotein receptor (LDLR) null mice as well as reducing the expression of an array of genes within the cholesterol biosynthetic pathway...
February 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28213091/convergence-of-hepcidin-deficiency-systemic-iron-overloading-heme-accumulation-and-rev-erb%C3%AE-%C3%AE-activation-in-aryl-hydrocarbon-receptor-elicited-hepatotoxicity
#10
Kelly A Fader, Rance Nault, Mathew P Kirby, Gena Markous, Jason Matthews, Timothy R Zacharewski
Persistent aryl hydrocarbon receptor (AhR) agonists elicit dose-dependent hepatic lipid accumulation, oxidative stress, inflammation, and fibrosis in mice. Iron (Fe) promotes AhR-mediated oxidative stress by catalyzing reactive oxygen species (ROS) production. To further characterize the role of Fe in AhR-mediated hepatotoxicity, male C57BL/6 mice were orally gavaged with sesame oil vehicle or 0.01-30μg/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) every 4days for 28days. Duodenal epithelial and hepatic RNA-Seq data were integrated with hepatic AhR ChIP-Seq, capillary electrophoresis protein measurements, and clinical chemistry analyses...
February 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28212627/genome-wide-identification-of-direct-hbx-genomic-targets
#11
Francesca Guerrieri, Laura Belloni, Daniel D'Andrea, Natalia Pediconi, Loredana Le Pera, Barbara Testoni, Cecilia Scisciani, Oceane Floriot, Fabien Zoulim, Anna Tramontano, Massimo Levrero
BACKGROUND: The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28211524/epigenetic-and-genetic-dissections-of-uv-induced-global-gene-dysregulation-in-skin-cells-through-multi-omics-analyses
#12
Yao Shen, Milda Stanislauskas, Gen Li, Deyou Zheng, Liang Liu
To elucidate the complex molecular mechanisms underlying the adverse effects UV radiation (UVR) on skin homeostasis, we performed multi-omics studies to characterize UV-induced genetic and epigenetic changes. Human keratinocytes from a single donor treated with or without UVR were analyzed by RNA-seq, exome-seq, and H3K27ac ChIP-seq at 4 h and 72 h following UVR. Compared to the relatively moderate mutagenic effects of UVR, acute UV exposure induced substantial epigenomic and transcriptomic alterations, illuminating a previously underappreciated role of epigenomic and transcriptomic instability in skin pathogenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#13
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28204599/cismapper-predicting-regulatory-interactions-from-transcription-factor-chip-seq-data
#14
Timothy O'Connor, Mikael Bodén, Timothy L Bailey
No abstract text is available yet for this article.
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28202838/role-of-ad4-binding-protein-steroidogenic-factor-1-in-regulating-nadph-production-in-adrenocortical-y-1-cells
#15
Bing Li, Takashi Baba, Kanako Miyabayashi, Tetsuya Sato, Yuichi Shima, Tomomi Ichinose, Daisuke Miura, Yasuyuki Ohkawa, Mikita Suyama, Ken-Ichirou Morohashi
Ad4-binding protein/steroidogenic factor 1 (Ad4BP/SF-1), a member of the nuclear receptor superfamily, is expressed in steroidogenic cells and regulates all steroidogenic gene expression. We recently employed mRNA and chromatin immunoprecipitation sequence (ChIP-seq) to demonstrate that Ad4BP/SF-1 directly regulates the expression of nearly all glycolytic genes. The pentose phosphate pathway (PPP) contributes to the production of nicotinamide adenine dinucleotide phosphate (NADPH). Although the expression of PPP genes and intracellular NADPH were decreased by Ad4BP/SF-1 knockdown, these genes were not the direct targets of Ad4BP/SF-1...
February 14, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28199841/lineage-specific-genes-are-prominent-dna-damage-hotspots-during-leukemic-transformation-of-b-cell-precursors
#16
Bryant Boulianne, Mark E Robinson, Philippa C May, Leandro Castellano, Kevin Blighe, Jennifer Thomas, Alistair Reid, Markus Müschen, Jane F Apperley, Justin Stebbing, Niklas Feldhahn
In human leukemia, lineage-specific genes represent predominant targets of deletion, with lymphoid-specific genes frequently affected in lymphoid leukemia and myeloid-specific genes in myeloid leukemia. To investigate the basis of lineage-specific alterations, we analyzed global DNA damage in primary B cell precursors expressing leukemia-inducing oncogenes by ChIP-seq. We identified more than 1,000 sensitive regions, of which B lineage-specific genes constitute the most prominent targets. Identified hotspots at B lineage genes relate to DNA-DSBs, affect genes that harbor genomic lesions in human leukemia, and associate with ectopic deletion in successfully transformed cells...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28187197/genetic-variants-alter-t-bet-binding-and-gene-expression-in-mucosal-inflammatory-disease
#17
Katrina Soderquest, Arnulf Hertweck, Claudia Giambartolomei, Stephen Henderson, Rami Mohamed, Rimma Goldberg, Esperanza Perucha, Lude Franke, Javier Herrero, Vincent Plagnol, Richard G Jenner, Graham M Lord
The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28186491/combinatorial-bzip-dimers-define-complex-dna-binding-specificity-landscapes
#18
Jose A Rodriguez-Martinez, Aaron W Reinke, Devesh Bhimsaria, Amy E Keating, Aseem Z Ansari
How transcription factor dimerization impacts DNA binding specificity is poorly understood. Guided by protein dimerization properties, we examined DNA binding specificities of 270 human bZIP pairs. DNA interactomes of 80 heterodimers and 22 homodimers revealed that 72% of heterodimer motifs correspond to conjoined half-sites preferred by partnering monomers. Remarkably, the remaining motifs are composed of variably-spaced half-sites (12%) or 'emergent' sites (16%) that cannot be readily inferred from half-site preferences of partnering monomers...
February 10, 2017: ELife
https://www.readbyqxmd.com/read/28181482/small-genomic-insertions-form-enhancers-that-misregulate-oncogenes
#19
Brian J Abraham, Denes Hnisz, Abraham S Weintraub, Nicholas Kwiatkowski, Charles H Li, Zhaodong Li, Nina Weichert-Leahey, Sunniyat Rahman, Yu Liu, Julia Etchin, Benshang Li, Shuhong Shen, Tong Ihn Lee, Jinghui Zhang, A Thomas Look, Marc R Mansour, Richard A Young
The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28178271/tead-transcription-factors-are-required-for-normal-primary-myoblast-differentiation-in-vitro-and-muscle-regeneration-in-vivo
#20
Shilpy Joshi, Guillaume Davidson, Stéphanie Le Gras, Shuichi Watanabe, Thomas Braun, Gabrielle Mengus, Irwin Davidson
The TEAD family of transcription factors (TEAD1-4) bind the MCAT element in the regulatory elements of both growth promoting and myogenic differentiation genes. Defining TEAD transcription factor function in myogenesis has proved elusive due to overlapping expression of family members and their functional redundancy. We show that silencing of either Tead1, Tead2 or Tead4 did not effect primary myoblast (PM) differentiation, but that their simultaneous knockdown strongly impaired differentiation. In contrast, Tead1 or Tead4 silencing impaired C2C12 differentiation showing their different contributions in PMs and C2C12 cells...
February 2017: PLoS Genetics
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