Heterochromatin spreading, the expansion of gene-silencing structures from DNA-encoded nucleation sites, occurs in distinct settings. Spreading re-establishes gene-poor constitutive heterochromatin every cell cycle, but also invades gene-rich euchromatin de novo to steer cell fate decisions. How chromatin context, i.e. euchromatic, heterochromatic, or different nucleator types, influences the determinants of this process remains poorly understood. By screening a nuclear function gene deletion library in fission yeast using a previously established heterochromatin spreading sensor system, we identified regulators that positively or negatively alter the propensity of a nucleation site to spread heterochromatin. We find that different chromatin contexts are dependent on unique sets of genes for the regulation of heterochromatin spreading. Further, we find that spreading in constitutive heterochromatin requires Clr6 histone deacetylase complexes containing the Fkh2 transcription factor, while the Clr3 deacetylase is globally required for silencing. Fkh2 acts by recruiting Clr6 to nucleation-distal chromatin sites. Our results segregate the pathways that control lateral heterochromatin spreading from those that instruct DNA-directed assembly in nucleation.

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局部染色质背景决定了异染色质扩散反应的遗传决定因素

异染色质扩散，即 DNA 编码成核位点的基因沉默结构的扩展，发生在不同的环境中。传播会在每个细胞周期重新建立缺乏基因的组成型异染色质，但也会从头侵入富含基因的常染色质以引导细胞命运决定。染色质背景（即常染色质、异染色质或不同的成核剂类型）如何影响该过程的决定因素仍然知之甚少。通过使用先前建立的异染色质扩散传感器系统筛选裂殖酵母中的核功能基因缺失库，我们确定了积极或消极改变成核位点扩散异染色质倾向的调节剂。我们发现不同的染色质背景依赖于独特的基因组来调节异染色质扩散。更远，我们发现在组成型异染色质中的扩散需要含有 Fkh2 转录因子的 Clr6 组蛋白脱乙酰酶复合物，而 Clr3 脱乙酰酶是全局沉默所必需的。Fkh2 通过将 Clr6 招募到成核远端染色质位点来发挥作用。我们的结果将控制横向异染色质扩散的途径与指导 DNA 定向组装成核的途径分开。