High-resolution DNA-binding specificity analysis of yeast transcription factors
| Autor: | Michael F. Berger, Marcin Pacek, Zachary A. Smith, Federico De Masi, Cong Zhu, Joshua LaBaer, Anthony A. Philippakis, Yanhui Hu, Rachel Patton McCord, T. V. S. Murthy, Daniel E. Newburger, Mathangi Radhakrishnan, Andreas Rolfs, Kelsey J. R. P. Byers, Zhenwei Shi, Katrina Saulrieta, Martha L. Bulyk, Mita V. Shah |
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| Přispěvatelé: | Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Smith, Zachary, Radhakrishnan, Mathangi, Philippakis, Anthony A., Bulyk, Martha L., Saulrieta, Katrina |
| Rok vydání: | 2009 |
| Předmět: |
Chromatin Immunoprecipitation
Saccharomyces cerevisiae Proteins Ribosome biogenesis Saccharomyces cerevisiae Regulatory Sequences Nucleic Acid Biology Response Elements Polymerase Chain Reaction DNA-binding protein Article Transcription (biology) Gene Expression Regulation Fungal Genetics Consensus sequence DNA Fungal Promoter Regions Genetic Gene Transcription factor Genetics (clinical) Oligonucleotide Array Sequence Analysis Binding Sites Gene Expression Profiling Computational Biology DNA-Binding Proteins Regulatory sequence Genome Fungal Chromatin immunoprecipitation Protein Binding Transcription Factors |
| Zdroj: | Genome Research |
| ISSN: | 1088-9051 |
| DOI: | 10.1101/gr.090233.108 |
| Popis: | Transcription factors (TFs) regulate the expression of genes through sequence-specific interactions with DNA-binding sites. However, despite recent progress in identifying in vivo TF binding sites by microarray readout of chromatin immunoprecipitation (ChIP-chip), nearly half of all known yeast TFs are of unknown DNA-binding specificities, and many additional predicted TFs remain uncharacterized. To address these gaps in our knowledge of yeast TFs and their cis regulatory sequences, we have determined high-resolution binding profiles for 89 known and predicted yeast TFs, over more than 2.3 million gapped and ungapped 8-bp sequences (“k-mers”). We report 50 new or significantly different direct DNA-binding site motifs for yeast DNA-binding proteins and motifs for eight proteins for which only a consensus sequence was previously known; in total, this corresponds to over a 50% increase in the number of yeast DNA-binding proteins with experimentally determined DNA-binding specificities. Among other novel regulators, we discovered proteins that bind the PAC (Polymerase A and C) motif (GATGAG) and regulate ribosomal RNA (rRNA) transcription and processing, core cellular processes that are constituent to ribosome biogenesis. In contrast to earlier data types, these comprehensive k-mer binding data permit us to consider the regulatory potential of genomic sequence at the individual word level. These k-mer data allowed us to reannotate in vivo TF binding targets as direct or indirect and to examine TFs' potential effects on gene expression in ∼1700 environmental and cellular conditions. These approaches could be adapted to identify TFs and cis regulatory elements in higher eukaryotes. National Institutes of Health (U.S.) (NIH/NHGRI grant R01 HG003985) National Institutes of Health (U.S.) (NIH/NHGRI grant R01 HG003420) National Science Foundation (U.S.) (NSF Graduate Research Fellowship) |
| Databáze: | OpenAIRE |
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