The Experts below are selected from a list of 96 Experts worldwide ranked by ideXlab platform
Dennis J Thiele - One of the best experts on this subject based on the ideXlab platform.
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genomic heat shock element sequences drive cooperative human heat shock factor 1 dna binding and selectivity
Journal of Biological Chemistry, 2014Co-Authors: Alex M Jaeger, Leah N Makley, Jason E Gestwicki, Dennis J ThieleAbstract:The heat shock transcription factor 1 (HSF1) activates expression of a variety of Genes involved in cell survival, including protein chaperones, the protein degradation machinery, anti-apoptotic proteins, and transcription factors. Although HSF1 activation has been linked to amelioration of neurodeGenerative disease, cancer cells exhibit a dependence on HSF1 for survival. Indeed, HSF1 drives a program of Gene expression in cancer cells that is distinct from that activated in response to proteotoxic stress, and HSF1 DNA binding activity is elevated in cycling cells as compared with arrested cells. Active HSF1 homotrimerizes and binds to a DNA sequence consisting of inverted repeats of the pentameric sequence nGAAn, known as heat shock elements (HSEs). Recent comprehensive ChIP-seq experiments demonstrated that the architecture of HSEs is very diverse in the human genome, with deviations from the consensus sequence in the spacing, orientation, and extent of HSE repeats that could influence HSF1 DNA binding efficacy and the kinetics and magnitude of target Gene expression. To understand the mechanisms that dictate binding specificity, HSF1 was purified as either a monomer or trimer and used to evaluate DNA-binding site preferences in vitro using fluorescence polarization and thermal denaturation profiling. These results were compared with quantitative chromatin immunoprecipitation assays in vivo. We demonstrate a role for specific orientations of extended HSE sequences in driving preferential HSF1 DNA binding to target loci in vivo. These studies provide a biochemical basis for understanding differential HSF1 target Gene Recognition and transcription in neurodeGenerative disease and in cancer.
Mikhail S Gelfand - One of the best experts on this subject based on the ideXlab platform.
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combining diverse evidence for Gene Recognition in completely sequenced bacterial genomes
Nucleic Acids Research, 1998Co-Authors: Dmitrij Frishman, Andrey A Mironov, Hanswerner Mewes, Mikhail S GelfandAbstract:Analysis of a newly sequenced bacterial genome starts with identification of protein-coding Genes. Functional assignment of proteins requires the exact knowledge of protein N-termini. We present a new program ORPHEUS that identifies candidate Genes and accurately predicts Gene starts. The analysis starts with a database similarity search and identification of reliable Gene fragments. The latter are used to derive statistical characteristics of protein-coding regions and ribosome-binding sites and to predict the complete set of Genes in the analyzed genome. In a test on Bacillus subtilis and Escherichia coli genomes, the program correctly identified 93.3% (resp. 96.3%) of experimentally annotated Genes longer than 100 codons described in the PIR-International database, and for these Genes 96.3% (83.9%) of starts were predicted exactly. Furthermore, 98.9% (99.1%) of Genes longer than 100 codons annotated in GenBank were found, and 92.9% (75.7%) of predicted starts coincided with the feature table description. Finally, for the complete Gene complements of B.subtilis and E.coli, including Genes shorter than 100 codons, Gene prediction accuracy was 88.9 and 87.1%, respectively, with 94.2 and 76.7% starts coinciding with the existing annotation.
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Gene Recognition via spliced sequence alignment
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Mikhail S Gelfand, Andrey A Mironov, Pavel A PevznerAbstract:Abstract Gene Recognition is one of the most important problems in computational molecular biology. Previous attempts to solve this problem were based on statistics, and applications of combinatorial methods for Gene Recognition were almost unexplored. Recent advances in large-scale cDNA sequencing open a way toward a new approach to Gene Recognition that uses previously sequenced Genes as a clue for Recognition of newly sequenced Genes. This paper describes a spliced alignment algorithm and software tool that explores all possible exon assemblies in polynomial time and finds the multiexon structure with the best fit to a related protein. Unlike other existing methods, the algorithm successfully recognizes Genes even in the case of short exons or exons with unusual codon usage; we also report correct assemblies for Genes with more than 10 exons. On a test sample of human Genes with known mammalian relatives, the average correlation between the predicted and actual proteins was 99%. The algorithm correctly reconstructed 87% of Genes and the rare discrepancies between the predicted and real exon-intron structures were caused either by short (less than 5 amino acids) initial/terminal exons or by alternative splicing. Moreover, the algorithm predicts human Genes reasonably well when the homologous protein is nonvertebrate or even prokaryotic. The surprisingly good performance of the method was confirmed by extensive simulations: in particular, with target proteins at 160 accepted point mutations (PAM) (25% similarity), the correlation between the predicted and actual Genes was still as high as 95%.
Alex M Jaeger - One of the best experts on this subject based on the ideXlab platform.
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genomic heat shock element sequences drive cooperative human heat shock factor 1 dna binding and selectivity
Journal of Biological Chemistry, 2014Co-Authors: Alex M Jaeger, Leah N Makley, Jason E Gestwicki, Dennis J ThieleAbstract:The heat shock transcription factor 1 (HSF1) activates expression of a variety of Genes involved in cell survival, including protein chaperones, the protein degradation machinery, anti-apoptotic proteins, and transcription factors. Although HSF1 activation has been linked to amelioration of neurodeGenerative disease, cancer cells exhibit a dependence on HSF1 for survival. Indeed, HSF1 drives a program of Gene expression in cancer cells that is distinct from that activated in response to proteotoxic stress, and HSF1 DNA binding activity is elevated in cycling cells as compared with arrested cells. Active HSF1 homotrimerizes and binds to a DNA sequence consisting of inverted repeats of the pentameric sequence nGAAn, known as heat shock elements (HSEs). Recent comprehensive ChIP-seq experiments demonstrated that the architecture of HSEs is very diverse in the human genome, with deviations from the consensus sequence in the spacing, orientation, and extent of HSE repeats that could influence HSF1 DNA binding efficacy and the kinetics and magnitude of target Gene expression. To understand the mechanisms that dictate binding specificity, HSF1 was purified as either a monomer or trimer and used to evaluate DNA-binding site preferences in vitro using fluorescence polarization and thermal denaturation profiling. These results were compared with quantitative chromatin immunoprecipitation assays in vivo. We demonstrate a role for specific orientations of extended HSE sequences in driving preferential HSF1 DNA binding to target loci in vivo. These studies provide a biochemical basis for understanding differential HSF1 target Gene Recognition and transcription in neurodeGenerative disease and in cancer.
Leah N Makley - One of the best experts on this subject based on the ideXlab platform.
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genomic heat shock element sequences drive cooperative human heat shock factor 1 dna binding and selectivity
Journal of Biological Chemistry, 2014Co-Authors: Alex M Jaeger, Leah N Makley, Jason E Gestwicki, Dennis J ThieleAbstract:The heat shock transcription factor 1 (HSF1) activates expression of a variety of Genes involved in cell survival, including protein chaperones, the protein degradation machinery, anti-apoptotic proteins, and transcription factors. Although HSF1 activation has been linked to amelioration of neurodeGenerative disease, cancer cells exhibit a dependence on HSF1 for survival. Indeed, HSF1 drives a program of Gene expression in cancer cells that is distinct from that activated in response to proteotoxic stress, and HSF1 DNA binding activity is elevated in cycling cells as compared with arrested cells. Active HSF1 homotrimerizes and binds to a DNA sequence consisting of inverted repeats of the pentameric sequence nGAAn, known as heat shock elements (HSEs). Recent comprehensive ChIP-seq experiments demonstrated that the architecture of HSEs is very diverse in the human genome, with deviations from the consensus sequence in the spacing, orientation, and extent of HSE repeats that could influence HSF1 DNA binding efficacy and the kinetics and magnitude of target Gene expression. To understand the mechanisms that dictate binding specificity, HSF1 was purified as either a monomer or trimer and used to evaluate DNA-binding site preferences in vitro using fluorescence polarization and thermal denaturation profiling. These results were compared with quantitative chromatin immunoprecipitation assays in vivo. We demonstrate a role for specific orientations of extended HSE sequences in driving preferential HSF1 DNA binding to target loci in vivo. These studies provide a biochemical basis for understanding differential HSF1 target Gene Recognition and transcription in neurodeGenerative disease and in cancer.
Jason E Gestwicki - One of the best experts on this subject based on the ideXlab platform.
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genomic heat shock element sequences drive cooperative human heat shock factor 1 dna binding and selectivity
Journal of Biological Chemistry, 2014Co-Authors: Alex M Jaeger, Leah N Makley, Jason E Gestwicki, Dennis J ThieleAbstract:The heat shock transcription factor 1 (HSF1) activates expression of a variety of Genes involved in cell survival, including protein chaperones, the protein degradation machinery, anti-apoptotic proteins, and transcription factors. Although HSF1 activation has been linked to amelioration of neurodeGenerative disease, cancer cells exhibit a dependence on HSF1 for survival. Indeed, HSF1 drives a program of Gene expression in cancer cells that is distinct from that activated in response to proteotoxic stress, and HSF1 DNA binding activity is elevated in cycling cells as compared with arrested cells. Active HSF1 homotrimerizes and binds to a DNA sequence consisting of inverted repeats of the pentameric sequence nGAAn, known as heat shock elements (HSEs). Recent comprehensive ChIP-seq experiments demonstrated that the architecture of HSEs is very diverse in the human genome, with deviations from the consensus sequence in the spacing, orientation, and extent of HSE repeats that could influence HSF1 DNA binding efficacy and the kinetics and magnitude of target Gene expression. To understand the mechanisms that dictate binding specificity, HSF1 was purified as either a monomer or trimer and used to evaluate DNA-binding site preferences in vitro using fluorescence polarization and thermal denaturation profiling. These results were compared with quantitative chromatin immunoprecipitation assays in vivo. We demonstrate a role for specific orientations of extended HSE sequences in driving preferential HSF1 DNA binding to target loci in vivo. These studies provide a biochemical basis for understanding differential HSF1 target Gene Recognition and transcription in neurodeGenerative disease and in cancer.