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"DNA shape"

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...
October 18, 2016: Current Opinion in Genetics & Development
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...
October 6, 2016: American Journal of Human Genetics
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
Anthony Mathelier, Beibei Xin, Tsu-Pei Chiu, Lin Yang, Remo Rohs, Wyeth W Wasserman
Interactions of transcription factors (TFs) with DNA comprise a complex interplay between base-specific amino acid contacts and readout of DNA structure. Recent studies have highlighted the complementarity of DNA sequence and shape in modeling TF binding in vitro. Here, we have provided a comprehensive evaluation of in vivo datasets to assess the predictive power obtained by augmenting various DNA sequence-based models of TF binding sites (TFBSs) with DNA shape features (helix twist, minor groove width, propeller twist, and roll)...
August 18, 2016: Cell Systems
Pei-Chen Peng, Saurabh Sinha
Prediction of gene expression levels driven by regulatory sequences is pivotal in genomic biology. A major focus in transcriptional regulation is sequence-to-expression modeling, which interprets the enhancer sequence based on transcription factor concentrations and DNA binding specificities and predicts precise gene expression levels in varying cellular contexts. Such models largely rely on the position weight matrix (PWM) model for DNA binding, and the effect of alternative models based on DNA shape remains unexplored...
July 27, 2016: Nucleic Acids Research
Rosario I Corona, Jun-Tao Guo
DNA-binding proteins play critical roles in biological processes including gene expression, DNA packaging and DNA repair. They bind to DNA target sequences with different degrees of binding specificity, ranging from highly specific (HS) to nonspecific (NS). Alterations of DNA-binding specificity, due to either genetic variation or somatic mutations, can lead to various diseases. In this study, a comparative analysis of protein-DNA complex structures was carried out to investigate the structural features that contribute to binding specificity...
August 2016: Proteins
Samir Merabet, Richard S Mann
Hox proteins are key regulatory transcription factors that act in different tissues of the embryo to provide specific spatial and temporal coordinates to each cell. These patterning functions often depend on the presence of the TALE-homeodomain class cofactors, which form cooperative DNA-binding complexes with all Hox proteins. How this family of cofactors contributes to the highly diverse and specific functions of Hox proteins in vivo remains an important unsolved question. We review here the most recent advances in understanding the molecular mechanisms underlying Hox-TALE function...
June 2016: Trends in Genetics: TIG
Chuanying Chen, B Montgomery Pettitt
The binding process of a protein with a DNA involves three stages: approach, encounter, and association. It has been known that the complexation of protein and DNA involves mutual conformational changes, especially for a specific sequence association. However, it is still unclear how the conformation and the information in the DNA sequences affects the binding process. What is the extent to which the DNA structure adopted in the complex is induced by protein binding, or is instead intrinsic to the DNA sequence? In this study, we used the multiscale simulation method to explore the binding process of a protein with DNA in terms of DNA sequence, conformation, and interactions...
February 2, 2016: Biophysical Journal
Walid A Al-Zyoud, Robert M G Hynson, Lorraine A Ganuelas, Adelle C F Coster, Anthony P Duff, Matthew A B Baker, Alastair G Stewart, Eleni Giannoulatou, Joshua W K Ho, Katharina Gaus, Dali Liu, Lawrence K Lee, Till Böcking
Mechanisms for transcription factor recognition of specific DNA base sequences are well characterized and recent studies demonstrate that the shape of these cognate binding sites is also important. Here, we uncover a new mechanism where the transcription factor GabR simultaneously recognizes two cognate binding sites and the shape of a 29 bp DNA sequence that bridges these sites. Small-angle X-ray scattering and multi-angle laser light scattering are consistent with a model where the DNA undergoes a conformational change to bend around GabR during binding...
February 18, 2016: Nucleic Acids Research
Olga Zanegina, Dmitriy Kirsanov, Eugene Baulin, Anna Karyagina, Andrei Alexeevski, Sergey Spirin
The recent upgrade of nucleic acid-protein interaction database (NPIDB, includes a newly elaborated classification of complexes of protein domains with double-stranded DNA and a classification of families of related complexes. Our classifications are based on contacting structural elements of both DNA: the major groove, the minor groove and the backbone; and protein: helices, beta-strands and unstructured segments. We took into account both hydrogen bonds and hydrophobic interaction...
January 4, 2016: Nucleic Acids Research
Gabriel E Zentner, Sivakanthan Kasinathan, Beibei Xin, Remo Rohs, Steven Henikoff
Chromatin endogenous cleavage (ChEC) uses fusion of a protein of interest to micrococcal nuclease (MNase) to target calcium-dependent cleavage to specific genomic loci in vivo. Here we report the combination of ChEC with high-throughput sequencing (ChEC-seq) to map budding yeast transcription factor (TF) binding. Temporal analysis of ChEC-seq data reveals two classes of sites for TFs, one displaying rapid cleavage at sites with robust consensus motifs and the second showing slow cleavage at largely unique sites with low-scoring motifs...
October 22, 2015: Nature Communications
Connor H Fortin, Katharina V Schulze, Gregory A Babbitt
BACKGROUND: It is now widely-accepted that DNA sequences defining DNA-protein interactions functionally depend upon local biophysical features of DNA backbone that are important in defining sites of binding interaction in the genome (e.g. DNA shape, charge and intrinsic dynamics). However, these physical features of DNA polymer are not directly apparent when analyzing and viewing Shannon information content calculated at single nucleobases in a traditional sequence logo plot. Thus, sequence logos plots are severely limited in that they convey no explicit information regarding the structural dynamics of DNA backbone, a feature often critical to binding specificity...
2015: Source Code for Biology and Medicine
Hui San Ong, Mohd Syafiq Rahim, Mohd Firdaus-Raih, Effirul Ikhwan Ramlan
The unique programmability of nucleic acids offers alternative in constructing excitable and functional nanostructures. This work introduces an autonomous protocol to construct DNA Tetris shapes (L-Shape, B-Shape, T-Shape and I-Shape) using modular DNA blocks. The protocol exploits the rich number of sequence combinations available from the nucleic acid alphabets, thus allowing for diversity to be applied in designing various DNA nanostructures. Instead of a deterministic set of sequences corresponding to a particular design, the protocol promotes a large pool of DNA shapes that can assemble to conform to any desired structures...
2015: PloS One
Iris Dror, Tamar Golan, Carmit Levy, Remo Rohs, Yael Mandel-Gutfreund
Transcriptional regulation requires the binding of transcription factors (TFs) to short sequence-specific DNA motifs, usually located at the gene regulatory regions. Interestingly, based on a vast amount of data accumulated from genomic assays, it has been shown that only a small fraction of all potential binding sites containing the consensus motif of a given TF actually bind the protein. Recent in vitro binding assays, which exclude the effects of the cellular environment, also demonstrate selective TF binding...
September 2015: Genome Research
Jichen Yang, Stephen A Ramsey
MOTIVATION: The position-weight matrix (PWM) is a useful representation of a transcription factor binding site (TFBS) sequence pattern because the PWM can be estimated from a small number of representative TFBS sequences. However, because the PWM probability model assumes independence between individual nucleotide positions, the PWMs for some TFs poorly discriminate binding sites from non-binding-sites that have similar sequence content. Since the local three-dimensional DNA structure ('shape') is a determinant of TF binding specificity and since DNA shape has a significant sequence-dependence, we combined DNA shape-derived features into a TF-generalized regulatory score and tested whether the score could improve PWM-based discrimination of TFBS from non-binding-sites...
November 1, 2015: Bioinformatics
Tsu-Pei Chiu, Lin Yang, Tianyin Zhou, Bradley J Main, Stephen C J Parker, Sergey V Nuzhdin, Thomas D Tullius, Remo Rohs
No abstract text is available yet for this article.
2015: Journal of Biomolecular Structure & Dynamics
Lin Yang, Iris Dror, Tianyin Zhou, Anthony Mathelier, Wyeth W Wasserman, Raluca Gordân, Remo Rohs
No abstract text is available yet for this article.
2015: Journal of Biomolecular Structure & Dynamics
Tianyin Zhou, Ning Shen, Lin Yang, Namiko Abe, John Horton, Richard S Mann, Harmen J Bussemaker, Raluca Gordân, Remo Rohs
No abstract text is available yet for this article.
2015: Journal of Biomolecular Structure & Dynamics
Sunil Kumar, Meredith Newby Spano, Dev P Arya
DNA-protein recognition has shown us the importance of DNA shapes in the recognition process. Specific high-affinity targeting of DNA shapes by small molecules is desirable for many biological applications that involve regulation of DNA based processes. Here, the effect of linker length and rigidity on the affinity of a conjugated neomycin dimer for a specific DNA shape (B* form) AT-rich DNA was explored. Binding constants approximating 10(8)M(-1) for optimal linker lengths of 18-19 atoms are reported herein...
July 1, 2015: Bioorganic & Medicinal Chemistry
Federico Comoglio, Tommy Schlumpf, Virginia Schmid, Remo Rohs, Christian Beisel, Renato Paro
At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, the genetic and chromatin features defining metazoan replication start sites remain largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and suggest that they transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites...
May 5, 2015: Cell Reports
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