University of Copenhagen, Niels Bohr Institute, Copenhagen 2100, Denmark.
University of Copenhagen, Department of Biology, Copenhagen 2200, Denmark.
Cell Rep. 2022 May 17;39(7):110828. doi: 10.1016/j.celrep.2022.110828.
Transcription factors can exert opposite effects depending on the chromosomal context. The fission yeast transcription factor Atf1 both activates numerous genes in response to stresses and mediates heterochromatic gene silencing in the mating-type region. Investigating this context dependency, we report here that the establishment of silent heterochromatin in the mating-type region occurs at a reduced rate in the absence of Atf1 binding. Quantitative modeling accounts for the observed establishment profiles by a combinatorial recruitment of histone-modifying enzymes: locally by Atf1 at two binding sites and over the whole region by dynamically appearing heterochromatic nucleosomes, a source of which is the RNAi-dependent cenH element. In the absence of Atf1 binding, the synergy is lost, resulting in a slow rate of heterochromatin formation. The system shows how DNA-binding proteins can influence local nucleosome states and thereby potentiate long-range positive feedback on histone-modification reactions to enable heterochromatin formation over large regions in a context-dependent manner.
转录因子可以根据染色体环境发挥相反的作用。裂殖酵母转录因子 Atf1 既能响应胁迫激活大量基因，又能在交配型区域中介导异染色质基因沉默。在研究这种上下文依赖性时，我们在此报告，在没有 Atf1 结合的情况下，交配型区域中沉默异染色质的建立速度会降低。定量建模通过组蛋白修饰酶的组合募集来解释观察到的建立谱：局部由两个结合位点的 Atf1 进行，整个区域由动态出现的异染色质核小体进行，其来源是 RNAi 依赖性 cenH 元件。在没有 Atf1 结合的情况下，协同作用丧失，导致异染色质形成速度缓慢。该系统展示了 DNA 结合蛋白如何影响局部核小体状态，从而增强组蛋白修饰反应的长程正反馈，从而以依赖于上下文的方式在大区域内形成异染色质。
