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https://www.readbyqxmd.com/read/27900343/divergence-and-rewiring-of-regulatory-networks-for-neural-development-between-human-and-other-species
#1
COMMENT
Ping Wang, Dejian Zhao, Shira Rockowitz, Deyou Zheng
Neural and brain development in human and other mammalian species are largely similar, but distinct features exist at the levels of macrostructure and underlying genetic control. Comparative studies of epigenetic regulation and transcription factor (TF) binding in humans, chimpanzees, rodents, and other species have found large differences in gene regulatory networks. A recent analysis of the cistromes of REST/NRSF, a critical transcriptional regulator for the nervous system, demonstrated that REST binding to syntenic genomic regions (i...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27848897/bioinformatics-and-drug-discovery
#2
Xuhua Xia
Bioinformatic analysis can not only accelerate drug target identification and drug candidate screening and refinement, but also facilitate characterization of side effects and predict drug resistance. High-throughput data such as genomic, epigenetic, genome architecture, cistromic, transcriptomic, proteomic, and ribosome profiling data have all made significant contribution to mechanism-based drug discovery and drug repurposing. Accumulation of protein and RNA structures, as well as development of homology modeling and protein structure simulation, coupled with large structure databases of small molecules and metabolites, paved the way for more realistic protein-ligand docking experiments and more informative virtual screening...
November 16, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27802171/cooperative-binding-of-ap-1-and-tead4-modulates-the-balance-between-vascular-smooth-muscle-and-hemogenic-cell-fate
#3
Nadine Obier, Pierre Cauchy, Salam A Assi, Jane Gilmour, Michael Lie-A-Ling, Monika Lichtinger, Maarten Hoogenkamp, Laura Noailles, Peter N Cockerill, Georges Lacaud, Valerie Kouskoff, Constanze Bonifer
The transmission of extracellular signals into the nucleus involves inducible transcription factors, but how different signalling pathways act in a cell type-specific fashion is poorly understood. Here, we studied the regulatory role of the AP-1 transcription factor family in blood development using embryonic stem cell differentiation coupled with genome-wide transcription factor binding and gene expression analyses. AP-1 factors respond to MAP kinase signalling and comprise dimers of FOS, ATF and JUN proteins...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27789702/cistrome-data-browser-a-data-portal-for-chip-seq-and-chromatin-accessibility-data-in-human-and-mouse
#4
Shenglin Mei, Qian Qin, Qiu Wu, Hanfei Sun, Rongbin Zheng, Chongzhi Zang, Muyuan Zhu, Jiaxin Wu, Xiaohui Shi, Len Taing, Tao Liu, Myles Brown, Clifford A Meyer, X Shirley Liu
Chromatin immunoprecipitation, DNase I hypersensitivity and transposase-accessibility assays combined with high-throughput sequencing enable the genome-wide study of chromatin dynamics, transcription factor binding and gene regulation. Although rapidly accumulating publicly available ChIP-seq, DNase-seq and ATAC-seq data are a valuable resource for the systematic investigation of gene regulation processes, a lack of standardized curation, quality control and analysis procedures have hindered extensive reuse of these data...
October 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27672034/crosstalk-between-androgen-and-pro-inflammatory-signaling-remodels-androgen-receptor-and-nf-%C3%AE%C2%BAb-cistrome-to-reprogram-the-prostate-cancer-cell-transcriptome
#5
Marjo Malinen, Einari A Niskanen, Minna U Kaikkonen, Jorma J Palvimo
Inflammatory processes and androgen signaling are critical for the growth of prostate cancer (PC), the most common cancer among males in Western countries. To understand the importance of potential interplay between pro-inflammatory and androgen signaling for gene regulation, we have interrogated the crosstalk between androgen receptor (AR) and NF-κB, a key transcriptional mediator of inflammatory responses, by utilizing genome-wide chromatin immunoprecipitation sequencing and global run-on sequencing in PC cells...
September 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27634452/cell-lineage-specificity-and-role-of-ap-1-in-the-prostate-fibroblast-androgen-receptor-cistrome
#6
Damien A Leach, Vasilios Panagopoulos, Claire Nash, Charlotte Bevan, Axel A Thomson, Luke A Selth, Grant Buchanan
Androgen receptor (AR) signalling in fibroblasts is important in prostate development and carcinogenesis, and is inversely related to prostate cancer mortality. However, the molecular mechanisms of AR action in fibroblasts and other non-epithelial cell types are largely unknown. The genome-wide DNA binding profile of AR in human prostate fibroblasts was identified by chromatin immunoprecipitation sequencing (ChIP-Seq), and found to be common to other fibroblast lines but disparate from AR cistromes of prostate cancer cells and tissue...
September 12, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27617304/epigenetic-remodeling-regulates-transcriptional-changes-between-ovarian-cancer-and-benign-precursors
#7
Kevin M Elias, Megan M Emori, Thomas Westerling, Henry Long, Anna Budina-Kolomets, Fugen Li, Emily MacDuffie, Michelle R Davis, Alexander Holman, Brian Lawney, Matthew L Freedman, John Quackenbush, Myles Brown, Ronny Drapkin
Regulation of lineage-restricted transcription factors has been shown to influence malignant transformation in several types of cancer. Whether similar mechanisms are involved in ovarian cancer pathogenesis is unknown. PAX8 is a nuclear transcription factor that controls the embryologic development of the Müllerian system, including the fallopian tubes. Recent studies have shown that fallopian tube secretory epithelial cells (FTSECs) give rise to the most common form of ovarian cancer, high-grade serous ovarian carcinomas (HGSOCs)...
August 18, 2016: JCI Insight
https://www.readbyqxmd.com/read/27610578/cistrome-and-epicistrome-features-shape-the-regulatory-dna-landscape
#8
Ronan C O'Malley, Shao-Shan Carol Huang, Liang Song, Mathew G Lewsey, Anna Bartlett, Joseph R Nery, Mary Galli, Andrea Gallavotti, Joseph R Ecker
No abstract text is available yet for this article.
September 8, 2016: Cell
https://www.readbyqxmd.com/read/27569350/vitamin-d-dependent-chromatin-association-of-ctcf-in-human-monocytes
#9
Antonio Neme, Sabine Seuter, Carsten Carlberg
CCCTC-binding factor (CTCF) is a transcription factor being involved in 3D chromatin organization and displays a highly conserved genome-wide binding pattern. In this study, we report the cistrome of CTCF in THP-1 human monocytes and confirm that from the 40,078 CTCF binding sites nearly 85% are identical with those found in K562 monocytes. Quadruplicate chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that at 2130 loci the association strenght of CTCF with genomic DNA was significantly (p<0...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27549193/comprehensive-analyses-of-tumor-immunity-implications-for-cancer-immunotherapy
#10
Bo Li, Eric Severson, Jean-Christophe Pignon, Haoquan Zhao, Taiwen Li, Jesse Novak, Peng Jiang, Hui Shen, Jon C Aster, Scott Rodig, Sabina Signoretti, Jun S Liu, X Shirley Liu
BACKGROUND: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. RESULTS: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches...
August 22, 2016: Genome Biology
https://www.readbyqxmd.com/read/27489947/the-estrogen-receptor-%C3%AE-cistrome-beyond-breast-cancer
#11
Marjolein Droog, Mark Mensink, Wilbert Zwart
Although many tissues express estrogen receptor (ER)α, most studies focus on breast cancer where ERα occupies just a small fraction of its total repertoire of potential DNA-binding sites, based on sequence. This raises the question: Can ERα occupy these other potential binding sites in a different context? Ligands, splice variants, posttranslational modifications, and acquired mutations of ERα affect its conformation, which may alter chromatin interactions. To date, literature describes the DNA-binding sites of ERα (the ERα cistrome) in breast, endometrium, liver, and bone, in which the receptor mainly binds to enhancers...
October 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/27466232/modeling-cis-regulation-with-a-compendium-of-genome-wide-histone-h3k27ac-profiles
#12
Su Wang, Chongzhi Zang, Tengfei Xiao, Jingyu Fan, Shenglin Mei, Qian Qin, Qiu Wu, Xujuan Li, Kexin Xu, Housheng Hansen He, Myles Brown, Clifford A Meyer, X Shirley Liu
Model-based analysis of regulation of gene expression (MARGE) is a framework for interpreting the relationship between the H3K27ac chromatin environment and differentially expressed gene sets. The framework has three main functions: MARGE-potential, MARGE-express, and MARGE-cistrome. MARGE-potential defines a regulatory potential (RP) for each gene as the sum of H3K27ac ChIP-seq signals weighted by a function of genomic distance from the transcription start site. The MARGE framework includes a compendium of RPs derived from 365 human and 267 mouse H3K27ac ChIP-seq data sets...
October 2016: Genome Research
https://www.readbyqxmd.com/read/27453575/integrative-functional-genomics-implicates-epb41-dysregulation-in-hepatocellular-carcinoma-risk
#13
Xinyu Yang, Dianke Yu, Yanli Ren, Jinyu Wei, Wenting Pan, Changchun Zhou, Liqing Zhou, Yu Liu, Ming Yang
Genome-wide association studies (GWASs) have provided many insights into cancer genetics. However, the molecular mechanisms of many susceptibility SNPs defined by GWASs in cancer heritability and in promoting cancer risk remain elusive. New research strategies, including functional evaluations, are warranted to systematically explore truly causal genetic variants. In this study, we developed an integrative functional genomics methodology to identify cancer susceptibility SNPs in transcription factor-binding sites across the whole genome...
August 4, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27419873/epigenomic-diversity-in-a-global-collection-of-arabidopsis-thaliana-accessions
#14
Taiji Kawakatsu, Shao-Shan Carol Huang, Florian Jupe, Eriko Sasaki, Robert J Schmitz, Mark A Urich, Rosa Castanon, Joseph R Nery, Cesar Barragan, Yupeng He, Huaming Chen, Manu Dubin, Cheng-Ruei Lee, Congmao Wang, Felix Bemm, Claude Becker, Ryan O'Neil, Ronan C O'Malley, Danjuma X Quarless, Nicholas J Schork, Detlef Weigel, Magnus Nordborg, Joseph R Ecker
The epigenome orchestrates genome accessibility, functionality, and three-dimensional structure. Because epigenetic variation can impact transcription and thus phenotypes, it may contribute to adaptation. Here, we report 1,107 high-quality single-base resolution methylomes and 1,203 transcriptomes from the 1001 Genomes collection of Arabidopsis thaliana. Although the genetic basis of methylation variation is highly complex, geographic origin is a major predictor of genome-wide DNA methylation levels and of altered gene expression caused by epialleles...
July 14, 2016: Cell
https://www.readbyqxmd.com/read/27402906/crispr-do-for-genome-wide-crispr-design-and-optimization
#15
Jian Ma, Johannes Köster, Qian Qin, Shengen Hu, Wei Li, Chenhao Chen, Qingyi Cao, Jinzeng Wang, Shenglin Mei, Qi Liu, Han Xu, Xiaole Shirley Liu
MOTIVATION: Despite the growing popularity in using CRISPR/Cas9 technology for genome editing and gene knockout, its performance still relies on well-designed single guide RNAs (sgRNA). In this study, we propose a web application for the Design and Optimization (CRISPR-DO) of guide sequences that target both coding and non-coding regions in spCas9 CRISPR system across human, mouse, zebrafish, fly and worm genomes. CRISPR-DO uses a computational sequence model to predict sgRNA efficiency, and employs a specificity scoring function to evaluate the potential of off-target effect...
November 1, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27203113/cistrome-and-epicistrome-features-shape-the-regulatory-dna-landscape
#16
Ronan C O'Malley, Shao-Shan Carol Huang, Liang Song, Mathew G Lewsey, Anna Bartlett, Joseph R Nery, Mary Galli, Andrea Gallavotti, Joseph R Ecker
The cistrome is the complete set of transcription factor (TF) binding sites (cis-elements) in an organism, while an epicistrome incorporates tissue-specific DNA chemical modifications and TF-specific chemical sensitivities into these binding profiles. Robust methods to construct comprehensive cistrome and epicistrome maps are critical for elucidating complex transcriptional networks that underlie growth, behavior, and disease. Here, we describe DNA affinity purification sequencing (DAP-seq), a high-throughput TF binding site discovery method that interrogates genomic DNA with in-vitro-expressed TFs...
May 19, 2016: Cell
https://www.readbyqxmd.com/read/27197205/multiplex-enhancer-reporter-assays-uncover-unsophisticated-tp53-enhancer-logic
#17
Annelien Verfaillie, Dmitry Svetlichnyy, Hana Imrichova, Kristofer Davie, Mark Fiers, Zeynep Kalender Atak, Gert Hulselmans, Valerie Christiaens, Stein Aerts
Transcription factors regulate their target genes by binding to regulatory regions in the genome. Although the binding preferences of TP53 are known, it remains unclear what distinguishes functional enhancers from nonfunctional binding. In addition, the genome is scattered with recognition sequences that remain unoccupied. Using two complementary techniques of multiplex enhancer-reporter assays, we discovered that functional enhancers could be discriminated from nonfunctional binding events by the occurrence of a single TP53 canonical motif...
July 2016: Genome Research
https://www.readbyqxmd.com/read/27197147/comparative-cistromics-reveals-genomic-cross-talk-between-foxa1-and-er%C3%AE-in-tamoxifen-associated-endometrial-carcinomas
#18
Marjolein Droog, Ekaterina Nevedomskaya, Yongsoo Kim, Tesa Severson, Koen D Flach, Mark Opdam, Karianne Schuurman, Patrycja Gradowska, Michael Hauptmann, Gwen Dackus, Harry Hollema, Marian Mourits, Petra Nederlof, Hester van Boven, Sabine C Linn, Lodewyk Wessels, Flora E van Leeuwen, Wilbert Zwart
Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer. ERα was found at active enhancers in endometrial cancer cells as marked by the presence of RNA polymerase II and the histone marker H3K27Ac...
July 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27164166/changes-in-gene-expression-and-estrogen-receptor-cistrome-in-mouse-liver-upon-acute-e2-treatment
#19
Gaëlle Palierne, Aurélie Fabre, Romain Solinhac, Christine Le Péron, Stéphane Avner, Françoise Lenfant, Coralie Fontaine, Gilles Salbert, Gilles Flouriot, Jean-François Arnal, Raphaël Métivier
Transcriptional regulation by the estrogen receptor-α (ER) has been investigated mainly in breast cancer cell lines, but estrogens such as 17β-estradiol (E2) exert numerous extrareproductive effects, particularly in the liver, where E2 exhibits both protective metabolic and deleterious thrombotic actions. To analyze the direct and early transcriptional effects of estrogens in the liver, we determined the E2-sensitive transcriptome and ER cistrome in mice after acute administration of E2 or placebo. These analyses revealed the early induction of genes involved in lipid metabolism, which fits with the crucial role of ER in the prevention of liver steatosis...
July 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/27137654/the-hematopoietic-stem-and-progenitor-cell-cistrome-gata-factor-dependent-cis-regulatory-mechanisms
#20
K J Hewitt, K D Johnson, X Gao, S Keles, E H Bresnick
Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies...
2016: Current Topics in Developmental Biology
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