Diverse DNA Sequence Motifs Activate Meiotic Recombination Hotspots Through a Common Chromatin Remodeling Pathway
| Autor: | Wayne P. Wahls, Reine U. Protacio, Tresor O. Mukiza, Mari K. Davidson, Walter W. Steiner |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Spo11 genetic processes information science Investigations urologic and male genital diseases Genetic recombination Chromatin remodeling chromatin remodeling Genome Integrity and Transmission 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Schizosaccharomyces Genetics Nucleosome Nucleotide Motifs Homologous Recombination 030304 developmental biology 0303 health sciences genetic recombination biology epigenetics nucleosome food and beverages biology.organism_classification Chromatin Assembly and Disassembly Chromatin Meiosis chemistry Schizosaccharomyces pombe biology.protein Schizosaccharomyces pombe Proteins Homologous recombination 030217 neurology & neurosurgery DNA Transcription Factors |
| Zdroj: | Genetics |
| ISSN: | 1943-2631 0016-6731 |
| Popis: | Homologous recombination is induced to high levels in meiosis and is clustered at hotspots that regulate its frequency and distribution in the genome. By studying five different classes of DNA sequence-dependent recombination hotspots in the fission yeast... In meiosis, multiple different DNA sequence motifs help to position homologous recombination at hotspots in the genome. How do the seemingly disparate cis-acting regulatory modules each promote locally the activity of the basal recombination machinery? We defined molecular mechanisms of action for five different hotspot-activating DNA motifs (M26, CCAAT, Oligo-C, 4095, 4156) located independently at the same site within the ade6 locus of the fission yeast Schizosaccharomyces pombe. Each motif promoted meiotic recombination (i.e., is active) within this context, and this activity required the respective binding proteins (transcription factors Atf1, Pcr1, Php2, Php3, Php5, Rst2). High-resolution analyses of chromatin structure by nucleosome scanning assays revealed that each motif triggers the displacement of nucleosomes surrounding the hotspot motif in meiosis. This chromatin remodeling required the respective sequence-specific binding proteins, was constitutive for two motifs, and was enhanced meiotically for three others. Hotspot activity of each motif strongly required the ATP-dependent chromatin remodeling enzyme Snf22 (Snf2/Swi2), with lesser dependence on Gcn5, Mst2, and Hrp3. These findings support a model in which most meiotic recombination hotspots are positioned by the binding of transcription factors to their respective DNA sites. The functional redundancy of multiple, sequence-specific protein–DNA complexes converges upon shared chromatin remodeling pathways that help provide the basal recombination machinery (Spo11/Rec12 complex) access to its DNA substrates within chromatin. |
| Databáze: | OpenAIRE |
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