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.

取决于染色体背景，转录因子可以发挥相反的作用。裂变酵母转录因子 Atf1 既激活了许多响应压力的基因，又介导了交配型区域的异染色质基因沉默。调查这种上下文依赖性，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以降低的速率发生。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概况：Atf1 在两个结合位点局部地通过动态出现的异染色质核小体在整个区域进行，其来源是依赖于 RNAi 的cenH元素。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变慢。该系统显示了 DNA 结合蛋白如何影响局部核小体状态，从而增强对组蛋白修饰反应的长程正反馈，从而以上下文相关的方式在大区域形成异染色质。