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.

中文翻译：

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不同的 DNA 序列基序通过共同的染色质重塑途径激活减数分裂重组热点。

同源重组在减数分裂中被诱导至高水平，并聚集在调节其频率和在基因组中分布的热点处。通过研究裂殖酵母中五种不同类别的 DNA 序列依赖性重组热点...在减数分裂中，多个不同的 DNA 序列基序有助于将同源重组定位在基因组的热点处。看似不同的顺式作用调节模块如何各自促进基础重组机制的局部活性？我们定义了五种不同热点激活 DNA 基序（M26、CCAAT、Oligo-C、4095、4156）的分子作用机制，这些基序独立位于裂殖酵母裂殖酵母 ade6 基因座内的同一位点。每个基序在此背景下促进减数分裂重组（即具有活性），并且这种活性需要相应的结合蛋白（转录因子 Atf1、Pcr1、Php2、Php3、Php5、Rst2）。通过核小体扫描测定对染色质结构进行高分辨率分析表明，每个基序都会触发减数分裂中热点基序周围核小体的位移。这种染色质重塑需要各自的序列特异性结合蛋白，是两个基序的组成部分，并且对于其他三个基序来说，减数分裂得到增强。每个基序的热点活性强烈需要 ATP 依赖性染色质重塑酶 Snf22 (Snf2/Swi2)，对 Gcn5、Mst2 和 Hrp3 的依赖性较小。这些发现支持了一种模型，其中大多数减数分裂重组热点是通过转录因子与其各自 DNA 位点的结合来定位的。多个序列特异性蛋白质-DNA 复合物的功能冗余汇聚在共享的染色质重塑途径上，帮助基础重组机制（Spo11/Rec12 复合物）访问染色质内的 DNA 底物。