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- Title
Diverse DNA Sequence Motifs Activate Meiotic Recombination Hotspots Through a Common Chromatin Remodeling Pathway.
- Authors
Mukiza, Tresor O.; Protacio, Reine U.; Davidson, Mari K.; Steiner, Walter W.; Wahls, Wayne P.
- Abstract
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, sequencespecific 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.
- Subjects
CHROMOSOME analysis; DNA analysis; ADENOSINE triphosphatase; BIOLOGICAL assay; CELL physiology; GENETICS; KARYOKINESIS; TRANSCRIPTION factors; YEAST; SEQUENCE analysis; EPIGENOMICS
- Publication
Genetics, 2019, Vol 213, Issue 3, p789
- ISSN
0016-6731
- Publication type
Article
- DOI
10.1534/genetics.119.302679