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https://www.readbyqxmd.com/read/29563167/genome-wide-determinants-of-sequence-specific-dna-binding-of-general-regulatory-factors
#1
Matthew J Rossi, William K M Lai, B Franklin Pugh
General regulatory factors (GRFs), such as Reb1, Abf1, Rap1, Mcm1, and Cbf1, positionally organize yeast chromatin through interactions with a core consensus DNA sequence. It is assumed that sequence recognition via direct base readout suffices for specificity and that spurious nonfunctional sites are rendered inaccessible by chromatin. We tested these assumptions through genome-wide mapping of GRFs in vivo and in purified biochemical systems at near-base pair (bp) resolution using several ChIP-exo-based assays...
March 21, 2018: Genome Research
https://www.readbyqxmd.com/read/29510689/comparison-of-discriminative-motif-optimization-using-matrix-and-dna-shape-based-models
#2
Shuxiang Ruan, Gary D Stormo
BACKGROUND: Transcription factor (TF) binding site specificity is commonly represented by some form of matrix model in which the positions in the binding site are assumed to contribute independently to the site's activity. The independence assumption is known to be an approximation, often a good one but sometimes poor. Alternative approaches have been developed that use k-mers (DNA "words" of length k) to account for the non-independence, and more recently DNA structural parameters have been incorporated into the models...
March 6, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29472273/a-unified-approach-for-quantifying-and-interpreting-dna-shape-readout-by-transcription-factors
#3
H Tomas Rube, Chaitanya Rastogi, Judith F Kribelbauer, Harmen J Bussemaker
Transcription factors (TFs) interpret DNA sequence by probing the chemical and structural properties of the nucleotide polymer. DNA shape is thought to enable a parsimonious representation of dependencies between nucleotide positions. Here, we propose a unified mathematical representation of the DNA sequence dependence of shape and TF binding, respectively, which simplifies and enhances analysis of shape readout. First, we demonstrate that linear models based on mononucleotide features alone account for 60-70% of the variance in minor groove width, roll, helix twist, and propeller twist...
February 22, 2018: Molecular Systems Biology
https://www.readbyqxmd.com/read/29409522/systematic-prediction-of-dna-shape-changes-due-to-cpg-methylation-explains-epigenetic-effects-on-protein-dna-binding
#4
Satyanarayan Rao, Tsu-Pei Chiu, Judith F Kribelbauer, Richard S Mann, Harmen J Bussemaker, Remo Rohs
BACKGROUND: DNA shape analysis has demonstrated the potential to reveal structure-based mechanisms of protein-DNA binding. However, information about the influence of chemical modification of DNA is limited. Cytosine methylation, the most frequent modification, represents the addition of a methyl group at the major groove edge of the cytosine base. In mammalian genomes, cytosine methylation most frequently occurs at CpG dinucleotides. In addition to changing the chemical signature of C/G base pairs, cytosine methylation can affect DNA structure...
February 6, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29390080/experimental-maps-of-dna-structure-at-nucleotide-resolution-distinguish-intrinsic-from-protein-induced-dna-deformations
#5
Robert N Azad, Dana Zafiropoulos, Douglas Ober, Yining Jiang, Tsu-Pei Chiu, Jared M Sagendorf, Remo Rohs, Thomas D Tullius
Recognition of DNA by proteins depends on DNA sequence and structure. Often unanswered is whether the structure of naked DNA persists in a protein-DNA complex, or whether protein binding changes DNA shape. While X-ray structures of protein-DNA complexes are numerous, the structure of naked cognate DNA is seldom available experimentally. We present here an experimental and computational analysis pipeline that uses hydroxyl radical cleavage to map, at single-nucleotide resolution, DNA minor groove width, a recognition feature widely exploited by proteins...
January 30, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165643/expanding-the-repertoire-of-dna-shape-features-for-genome-scale-studies-of-transcription-factor-binding
#6
Jinsen Li, Jared M Sagendorf, Tsu-Pei Chiu, Marco Pasi, Alberto Perez, Remo Rohs
Uncovering the mechanisms that affect the binding specificity of transcription factors (TFs) is critical for understanding the principles of gene regulation. Although sequence-based models have been used successfully to predict TF binding specificities, we found that including DNA shape information in these models improved their accuracy and interpretability. Previously, we developed a method for modeling DNA binding specificities based on DNA shape features extracted from Monte Carlo (MC) simulations. Prediction accuracies of our models, however, have not yet been compared to accuracies of models incorporating DNA shape information extracted from X-ray crystallography (XRC) data or Molecular Dynamics (MD) simulations...
December 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29040720/genome-wide-prediction-of-minor-groove-electrostatic-potential-enables-biophysical-modeling-of-protein-dna-binding
#7
Tsu-Pei Chiu, Satyanarayan Rao, Richard S Mann, Barry Honig, Remo Rohs
Protein-DNA binding is a fundamental component of gene regulatory processes, but it is still not completely understood how proteins recognize their target sites in the genome. Besides hydrogen bonding in the major groove (base readout), proteins recognize minor-groove geometry using positively charged amino acids (shape readout). The underlying mechanism of DNA shape readout involves the correlation between minor-groove width and electrostatic potential (EP). To probe this biophysical effect directly, rather than using minor-groove width as an indirect measure for shape readout, we developed a methodology, DNAphi, for predicting EP in the minor groove and confirmed the direct role of EP in protein-DNA binding using massive sequencing data...
December 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28927002/predicting-variation-of-dna-shape-preferences-in-protein-dna-interaction-in-cancer-cells-with-a-new-biophysical-model
#8
Kirill Batmanov, Junbai Wang
DNA shape readout is an important mechanism of transcription factor target site recognition, in addition to the sequence readout. Several machine learning-based models of transcription factor-DNA interactions, considering DNA shape features, have been developed in recent years. Here, we present a new biophysical model of protein-DNA interactions by integrating the DNA shape properties. It is based on the neighbor dinucleotide dependency model BayesPI2, where new parameters are restricted to a subspace spanned by the dinucleotide form of DNA shape features...
September 18, 2017: Genes
https://www.readbyqxmd.com/read/28676789/importance-of-the-sequence-directed-dna-shape-for-specific-binding-site-recognition-by-the-estrogen-related-receptor
#9
Kareem Mohideen-Abdul, Karima Tazibt, Maxime Bourguet, Isabelle Hazemann, Isabelle Lebars, Maria Takacs, Sarah Cianférani, Bruno P Klaholz, Dino Moras, Isabelle M L Billas
Most nuclear receptors (NRs) bind DNA as dimers, either as hetero- or as homodimers on DNA sequences organized as two half-sites with specific orientation and spacing. The dimerization of NRs on their cognate response elements (REs) involves specific protein-DNA and protein-protein interactions. The estrogen-related receptor (ERR) belongs to the steroid hormone nuclear receptor (SHR) family and shares strong similarity in its DNA-binding domain (DBD) with that of the estrogen receptor (ER). In vitro, ERR binds with high affinity inverted repeat REs with a 3-bps spacing (IR3), but in vivo, it preferentially binds to single half-site REs extended at the 5'-end by 3 bp [estrogen-related response element (ERREs)], thus explaining why ERR was often inferred as a purely monomeric receptor...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28642456/predicting-conformational-ensembles-and-genome-wide-transcription-factor-binding-sites-from-dna-sequences
#10
Munazah Andrabi, Andrew Paul Hutchins, Diego Miranda-Saavedra, Hidetoshi Kono, Ruth Nussinov, Kenji Mizuguchi, Shandar Ahmad
DNA shape is emerging as an important determinant of transcription factor binding beyond just the DNA sequence. The only tool for large scale DNA shape estimates, DNAshape was derived from Monte-Carlo simulations and predicts four broad and static DNA shape features, Propeller twist, Helical twist, Minor groove width and Roll. The contributions of other shape features e.g. Shift, Slide and Opening cannot be evaluated using DNAshape. Here, we report a novel method DynaSeq, which predicts molecular dynamics-derived ensembles of a more exhaustive set of DNA shape features...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28631437/control-of-virulence-gene-transcription-by-indirect-readout-in-vibrio-cholerae-and-salmonella-enterica-serovar-typhimurium
#11
REVIEW
Charles J Dorman, Matthew J Dorman
Indirect readout mechanisms of transcription control rely on the recognition of DNA shape by transcription factors (TFs). TFs may also employ a direct readout mechanism that involves the reading of the base sequence in the DNA major groove at the binding site. TFs with winged helix-turn-helix (wHTH) motifs use an alpha helix to read the base sequence in the major groove while inserting a beta sheet 'wing' into the adjacent minor groove. Such wHTH proteins are important regulators of virulence gene transcription in many pathogens; they also control housekeeping genes...
October 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28580956/correspondence-dna-shape-is-insufficient-to-explain-binding
#12
Matthew J Rossi, William K M Lai, B Franklin Pugh
No abstract text is available yet for this article.
June 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28580953/correspondence-reply-to-dna-shape-is-insufficient-to-explain-binding
#13
Sivakanthan Kasinathan, Gabriel E Zentner, Beibei Xin, Remo Rohs, Steven Henikoff
No abstract text is available yet for this article.
June 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28541376/dna-sequence-shape-kernel-enables-alignment-free-modeling-of-transcription-factor-binding
#14
Wenxiu Ma, Lin Yang, Remo Rohs, William Stafford Noble
Motivation: Transcription factors (TFs) bind to specific DNA sequence motifs. Several lines of evidence suggest that TF-DNA binding is mediated in part by properties of the local DNA shape: the width of the minor groove, the relative orientations of adjacent base pairs, etc. Several methods have been developed to jointly account for DNA sequence and shape properties in predicting TF binding affinity. However, a limitation of these methods is that they typically require a training set of aligned TF binding sites...
October 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28355537/ephemeral-protein-binding-to-dna-shapes-stable-nuclear-bodies-and-chromatin-domains
#15
Chris A Brackley, Benno Liebchen, Davide Michieletto, Francois Mouvet, Peter R Cook, Davide Marenduzzo
Fluorescence microscopy reveals that the contents of many (membrane-free) nuclear bodies exchange rapidly with the soluble pool while the underlying structure persists; such observations await a satisfactory biophysical explanation. To shed light on this, we perform large-scale Brownian dynamics simulations of a chromatin fiber interacting with an ensemble of (multivalent) DNA-binding proteins able to switch between an "on" (binding) and an "off" (nonbinding) state. This system provides a model for any DNA-binding protein that can be posttranslationally modified to change its affinity for DNA (e...
March 28, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28167566/transcription-factor-family-specific-dna-shape-readout-revealed-by-quantitative-specificity-models
#16
Lin Yang, Yaron Orenstein, Arttu Jolma, Yimeng Yin, Jussi Taipale, Ron Shamir, Remo Rohs
Transcription factors (TFs) achieve DNA-binding specificity through contacts with functional groups of bases (base readout) and readout of structural properties of the double helix (shape readout). Currently, it remains unclear whether DNA shape readout is utilized by only a few selected TF families, or whether this mechanism is used extensively by most TF families. We resequenced data from previously published HT-SELEX experiments, the most extensive mammalian TF-DNA binding data available to date. Using these data, we demonstrated the contributions of DNA shape readout across diverse TF families and its importance in core motif-flanking regions...
February 6, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/27830804/evolution-cat-dna-shaped-by-diet
#17
(no author information available yet)
No abstract text is available yet for this article.
November 10, 2016: Nature
https://www.readbyqxmd.com/read/27768937/homeodomain-proteins-in-action-similar-dna-binding-preferences-highly-variable-connectivity
#18
REVIEW
Nicoletta Bobola, Samir Merabet
Homeodomain proteins are evolutionary conserved proteins present in the entire eukaryote kingdom. They execute functions that are essential for life, both in developing and adult organisms. Most homeodomain proteins act as transcription factors and bind DNA to control the activity of other genes. In contrast to their similar DNA binding specificity, homeodomain proteins execute highly diverse and context-dependent functions. Several factors, including genome accessibility, DNA shape, combinatorial binding and the ability to interact with many transcriptional partners, diversify the activity of homeodomain proteins and culminate in the activation of highly dynamic, context-specific transcriptional programs...
April 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/27745836/comprehensive-genetic-landscape-of-uveal-melanoma-by-whole-genome-sequencing
#19
Beryl Royer-Bertrand, Matteo Torsello, Donata Rimoldi, Ikram El Zaoui, Katarina Cisarova, Rosanna Pescini-Gobert, Franck Raynaud, Leonidas Zografos, Ann Schalenbourg, Daniel Speiser, Michael Nicolas, Laureen Vallat, Robert Klein, Serge Leyvraz, Giovanni Ciriello, Nicolò Riggi, Alexandre P Moulin, Carlo Rivolta
Uveal melanoma (UM) is a rare intraocular tumor that, similar to cutaneous melanoma, originates from melanocytes. To gain insights into its genetics, we performed whole-genome sequencing at very deep coverage of tumor-control pairs in 33 samples (24 primary and 9 metastases). Genome-wide, the number of coding mutations was rather low (only 17 variants per tumor on average; range 7-28), thus radically different from cutaneous melanoma, where hundreds of exonic DNA insults are usually detected. Furthermore, no UV light-induced mutational signature was identified...
November 3, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27569553/self-assembly-programming-of-dna-polyominoes
#20
Hui San Ong, Mohd Syafiq-Rahim, Noor Hayaty Abu Kasim, Mohd Firdaus-Raih, Effirul Ikhwan Ramlan
Fabrication of functional DNA nanostructures operating at a cellular level has been accomplished through molecular programming techniques such as DNA origami and single-stranded tiles (SST). During implementation, restrictive and constraint dependent designs are enforced to ensure conformity is attainable. We propose a concept of DNA polyominoes that promotes flexibility in molecular programming. The fabrication of complex structures is achieved through self-assembly of distinct heterogeneous shapes (i.e., self-organised optimisation among competing DNA basic shapes) with total flexibility during the design and assembly phases...
October 20, 2016: Journal of Biotechnology
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