The canonical BRG/BRM-associated factor (cBAF) complex is essential for chromatin opening at enhancers in mammalian cells. However, the nature of the open chromatin remains unclear. Here, we show that, in addition to producing histone-free DNA, cBAF generates stable hemisome-like subnucleosomal particles containing the four core histones associated with 50–80 bp of DNA. Our genome-wide analysis indicates that cBAF makes these particles by targeting and splitting fragile nucleosomes. In mouse embryonic stem cells, these subnucleosomes become an in vivo binding substrate for the master transcription factor OCT4 independently of the presence of OCT4 DNA motifs. At enhancers, the OCT4–subnucleosome interaction increases OCT4 occupancy and amplifies the genomic interval bound by OCT4 by up to one order of magnitude compared to the region occupied on histone-free DNA. We propose that cBAF-dependent subnucleosomes orchestrate a molecular mechanism that projects OCT4 function in chromatin opening beyond its DNA motifs.

典型的 BRG/BRM 相关因子 (cBAF) 复合物对于哺乳动物细胞增强子处染色质的打开至关重要。然而，开放染色质的性质仍不清楚。在这里，我们发现，除了产生无组蛋白的 DNA 之外，cBAF 还产生稳定的半体样亚核小体颗粒，其中含有与 50-80 bp DNA 相关的四种核心组蛋白。我们的全基因组分析表明，cBAF 通过靶向和分裂脆弱的核小体来制造这些颗粒。在小鼠胚胎干细胞中，这些亚核小体成为主转录因子 OCT4 的体内结合底物，与 OCT4 DNA 基序的存在无关。在增强子处，OCT4-亚核小体相互作用增加了 OCT4 占用率，并将 OCT4 结合的基因组间隔放大了一个数量级，与无组蛋白 DNA 上占用的区域相比。我们提出，cBAF 依赖性亚核小体协调了一种分子机制，将 OCT4 功能投射到 DNA 基序之外的染色质开放中。