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Transcriptional grammar

Xin Wang, Peijie Lin, Joshua W K Ho
BACKGROUND: It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types...
January 19, 2018: BMC Genomics
Adam G Diehl, Alan P Boyle
The mouse is widely used as system to study human genetic mechanisms. However, extensive rewiring of transcriptional regulatory networks often confounds translation of findings between human and mouse. Site-specific gain and loss of individual transcription factor binding sites (TFBS) has caused functional divergence of orthologous regulatory loci, and so we must look beyond this positional conservation to understand common themes of regulatory control. Fortunately, transcription factor co-binding patterns shared across species often perform conserved regulatory functions...
February 28, 2018: Nucleic Acids Research
Laurel A Coons, Sylvia C Hewitt, Adam B Burkholder, Donald P McDonnell, Kenneth S Korach
Gene regulatory programs are encoded in the sequence of the DNA. Since the completion of the Human Genome Project, millions of gene regulatory elements have been identified in the human genome. Understanding how each of those sites functionally contributes to gene regulation, however, remains a challenge for nearly every field of biology. Transcription factors influence cell function by interpreting information contained within cis-regulatory elements in chromatin. Whereas chromatin immunoprecipitation-sequencing has been used to identify and map transcription factor-DNA interactions, it has been difficult to assign functionality to the binding sites identified...
October 1, 2017: Endocrinology
Christopher M Vockley, Ian C McDowell, Antony M D'Ippolito, Timothy E Reddy
Gene regulation is fundamentally important for the coordination of diverse biologic processes including homeostasis and responses to developmental and environmental stimuli. Transcription factor (TF) binding sites are one of the major functional subunits of gene regulation. They are arranged in cis-regulatory modules (CRMs) that can be more active than the sum of their individual effects. Recently, we described a mechanism of glucocorticoid (GC)-induced gene regulation in which the glucocorticoid receptor (GR) binds coordinately to multiple CRMs that are 10s of kilobases apart in the genome...
August 8, 2017: Transcription
Haitao Guo, Hongwei Huo
The discovery of cis-regulatory modules (CRMs) is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs...
2017: BioMed Research International
Andrew E O Hughes, Jennifer M Enright, Connie A Myers, Susan Q Shen, Joseph C Corbo
Rod photoreceptors are specialized neurons that mediate vision in dim light and are the predominant photoreceptor type in nocturnal mammals. The rods of nocturnal mammals are unique among vertebrate cell types in having an 'inverted' nuclear architecture, with a dense mass of heterochromatin in the center of the nucleus rather than dispersed clumps at the periphery. To test if this unique nuclear architecture is correlated with a unique epigenomic landscape, we performed ATAC-seq on mouse rods and their most closely related cell type, cone photoreceptors...
March 3, 2017: Scientific Reports
Arushi Varshney, Laura J Scott, Ryan P Welch, Michael R Erdos, Peter S Chines, Narisu Narisu, Ricardo D'O Albanus, Peter Orchard, Brooke N Wolford, Romy Kursawe, Swarooparani Vadlamudi, Maren E Cannon, John P Didion, John Hensley, Anthony Kirilusha, Lori L Bonnycastle, D Leland Taylor, Richard Watanabe, Karen L Mohlke, Michael Boehnke, Francis S Collins, Stephen C J Parker, Michael L Stitzel
Genome-wide association studies (GWAS) have identified >100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, the pathogenic mechanisms of most of these SNPs remain elusive. Here, we examined genomic, epigenomic, and transcriptomic profiles in human pancreatic islets to understand the links between genetic variation, chromatin landscape, and gene expression in the context of T2D. We first integrated genome and transcriptome variation across 112 islet samples to produce dense cis -expression quantitative trait loci ( cis -eQTL) maps...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
Elise Drijbooms, Margriet A Groen, Ludo Verhoeven
The aim of this study was to examine the contribution of transcription skills, oral language skills, and executive functions to growth in narrative writing between fourth and sixth grade. While text length and story content of narratives did not increase with age, syntactic complexity of narratives showed a clear developmental progression. Results from path analyses revealed that later syntactic complexity of narrative writing was, in addition to initial syntactic complexity, predicted by oral grammar, inhibition, and planning...
2017: Reading and Writing
Sharon R Grossman, Xiaolan Zhang, Li Wang, Jesse Engreitz, Alexandre Melnikov, Peter Rogov, Ryan Tewhey, Alina Isakova, Bart Deplancke, Bradley E Bernstein, Tarjei S Mikkelsen, Eric S Lander
Enhancers regulate gene expression through the binding of sequence-specific transcription factors (TFs) to cognate motifs. Various features influence TF binding and enhancer function-including the chromatin state of the genomic locus, the affinities of the binding site, the activity of the bound TFs, and interactions among TFs. However, the precise nature and relative contributions of these features remain unclear. Here, we used massively parallel reporter assays (MPRAs) involving 32,115 natural and synthetic enhancers, together with high-throughput in vivo binding assays, to systematically dissect the contribution of each of these features to the binding and activity of genomic regulatory elements that contain motifs for PPARγ, a TF that serves as a key regulator of adipogenesis...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Michael A White, Jamie C Kwasnieski, Connie A Myers, Susan Q Shen, Joseph C Corbo, Barak A Cohen
Transcription factors often activate and repress different target genes in the same cell. How activation and repression are encoded by different arrangements of transcription factor binding sites in cis-regulatory elements is poorly understood. We investigated how sites for the transcription factor CRX encode both activation and repression in photoreceptors by assaying thousands of genomic and synthetic cis-regulatory elements in wild-type and Crx-/- retinas. We found that sequences with high affinity for CRX repress transcription, whereas sequences with lower affinity activate...
October 25, 2016: Cell Reports
R E Motyer, S Liddy, W C Torreggiani, O Buckley
BACKGROUND: Voice recognition (VR) dictation of radiology reports has become the mainstay of reporting in many institutions worldwide. Despite benefit, such software is not without limitations, and transcription errors have been widely reported. AIM: Evaluate the frequency and nature of non-clinical transcription error using VR dictation software. METHODS: Retrospective audit of 378 finalised radiology reports. Errors were counted and categorised by significance, error type and sub-type...
November 2016: Irish Journal of Medical Science
Ashley J Waardenberg, Bernou Homan, Stephanie Mohamed, Richard P Harvey, Romaric Bouveret
The ability to accurately predict the DNA targets and interacting cofactors of transcriptional regulators from genome-wide data can significantly advance our understanding of gene regulatory networks. NKX2-5 is a homeodomain transcription factor that sits high in the cardiac gene regulatory network and is essential for normal heart development. We previously identified genomic targets for NKX2-5 in mouse HL-1 atrial cardiomyocytes using DNA-adenine methyltransferase identification (DamID). Here, we apply machine learning algorithms and propose a knowledge-based feature selection method for predicting NKX2-5 protein : protein interactions based on motif grammar in genome-wide DNA-binding data...
September 2016: Open Biology
Rupinder Sayal, Jacqueline M Dresch, Irina Pushel, Benjamin R Taylor, David N Arnosti
Enhancers constitute one of the major components of regulatory machinery of metazoans. Although several genome-wide studies have focused on finding and locating enhancers in the genomes, the fundamental principles governing their internal architecture and cis-regulatory grammar remain elusive. Here, we describe an extensive, quantitative perturbation analysis targeting the dorsal-ventral patterning gene regulatory network (GRN) controlled by Drosophila NF-κB homolog Dorsal. To understand transcription factor interactions on enhancers, we employed an ensemble of mathematical models, testing effects of cooperativity, repression, and factor potency...
May 6, 2016: ELife
Brian MacWhinney, Davida Fromm
AphasiaBank has used a standardized protocol to collect narrative, procedural, personal, and descriptive discourse from 290 persons with aphasia, as well as 190 control participants. These data have been transcribed in the Codes for the Human Analysis of Transcripts (CHAT) format for analysis by the Computerized Language Analysis (CLAN) programs. Here, we review results from 45 studies based on these data that investigate aphasic productions in terms of these eight areas: discourse, grammar, lexicon, gesture, fluency, syndrome classification, social factors, and treatment effects...
February 2016: Seminars in Speech and Language
Joseph Grice, Boris Noyvert, Laura Doglio, Greg Elgar
BACKGROUND: Determining the function of regulatory elements is fundamental for our understanding of development, disease and evolution. However, the sequence features that mediate these functions are often unclear and the prediction of tissue-specific expression patterns from sequence alone is non-trivial. Previous functional studies have demonstrated a link between PBX-HOX and MEIS/PREP binding interactions and hindbrain enhancer activity, but the defining grammar of these sites, if any exists, has remained elusive...
2015: PloS One
Aliccia Bollig-Fischer, Luca Marchetti, Cristina Mitrea, Jiusheng Wu, Adéle Kruger, Vincenzo Manca, Sorin Drăghici
MOTIVATION: Oncogenes are known drivers of cancer phenotypes and targets of molecular therapies; however, the complex and diverse signaling mechanisms regulated by oncogenes and potential routes to targeted therapy resistance remain to be fully understood. To this end, we present an approach to infer regulatory mechanisms downstream of the HER2 driver oncogene in SUM-225 metastatic breast cancer cells from dynamic gene expression patterns using a succession of analytical techniques, including a novel MP grammars method to mathematically model putative regulatory interactions among sets of clustered genes...
November 1, 2014: Bioinformatics
Lucy Hiscox, Erika Leonavičiūtė, Trevor Humby
Dyslexia is associated with difficulties in language-specific skills such as spelling, writing and reading; the difficulty in acquiring literacy skills is not a result of low intelligence or the absence of learning opportunity, but these issues will persist throughout life and could affect long-term education. Writing is a complex process involving many different functions, integrated by the working memory system; people with dyslexia have a working memory deficit, which means that concentration on writing quality may be detrimental to understanding...
August 2014: Dyslexia: the Journal of the British Dyslexia Association
Oliver Purcell, Jean Peccoud, Timothy K Lu
To design and build living systems, synthetic biologists have at their disposal an increasingly large library of naturally derived and synthetic parts. These parts must be combined together in particular orders, orientations, and spacings to achieve desired functionalities. These structural constraints can be viewed as grammatical rules describing how to assemble parts together into larger functional units. Here, we develop a grammar for the design of synthetic transcription factors (sTFs) in eukaryotic cells and implement it within GenoCAD, a Computer-Aided Design (CAD) software for synthetic biology...
October 17, 2014: ACS Synthetic Biology
Vanja Haberle, Nan Li, Yavor Hadzhiev, Charles Plessy, Christopher Previti, Chirag Nepal, Jochen Gehrig, Xianjun Dong, Altuna Akalin, Ana Maria Suzuki, Wilfred F J van IJcken, Olivier Armant, Marco Ferg, Uwe Strähle, Piero Carninci, Ferenc Müller, Boris Lenhard
A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs and recruits general transcription factors to initiate transcription. The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle. Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition...
March 20, 2014: Nature
Shira Weingarten-Gabbay, Eran Segal
Eukaryotes employ combinatorial strategies to generate a variety of expression patterns from a relatively small set of regulatory DNA elements. As in any other language, deciphering the mapping between DNA and expression requires an understanding of the set of rules that govern basic principles in transcriptional regulation, the functional elements involved, and the ways in which they combine to orchestrate a transcriptional output. Here, we review the current understanding of various grammatical rules, including the effect on expression of the number of transcription factor binding sites, their location, orientation, affinity and activity; co-association with different factors; and intrinsic nucleosome organization...
June 2014: Human Genetics
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