CD8+T细胞通过分化为不同的效应细胞和记忆细胞亚群提供针对病原体的宿主保护。但染色质在分化过程中如何被位点特异性地重塑尚不清楚.由于其在通过核小体重塑活性调节染色质和增强子可及性方面的关键作用,我们研究了典型BAF(cBAF)染色质重塑复合物在感染期间抗病毒CD8+T细胞中的作用。ARID1A,cBAF的一个亚基,在激活后早期招募,并在增强子处建立从头开放染色质区(OCR)。Arid1a缺乏损害了数千种激活诱导的增强剂的开放,导致TF结合的丧失,增殖和基因表达失调,并不能进行终末效应子分化。尽管Arid1a对于循环记忆细胞的形成是不必要的,组织驻留记忆(Trm)形成严重受损。因此,cBAF控制着激活的CD8+T细胞的增强子景观,其协调TF募集和活性以及特定效应和记忆分化状态的获得。
CD8+ T cells provide host protection against pathogens by differentiating into distinct effector and memory cell subsets, but how chromatin is site-specifically remodeled during their differentiation is unclear. Due to its critical role in regulating chromatin and enhancer accessibility through its nucleosome remodeling activities, we investigated the role of the canonical BAF (cBAF) chromatin remodeling complex in antiviral CD8+ T cells during infection. ARID1A, a subunit of cBAF, was recruited early after activation and established de novo open chromatin regions (OCRs) at enhancers. Arid1a deficiency impaired the opening of thousands of activation-induced enhancers, leading to loss of TF binding, dysregulated proliferation and gene expression, and failure to undergo terminal effector differentiation. Although Arid1a was dispensable for circulating memory cell formation, tissue-resident memory (Trm) formation was strongly impaired. Thus, cBAF governs the enhancer landscape of activated CD8+ T cells that orchestrates TF recruitment and activity and the acquisition of specific effector and memory differentiation states.