The establishment of de novo chromatin accessibility in lymphoid progenitors requires the “pioneering” function of transcription factor (TF) early B cell factor 1 (EBF1), which binds to naïve chromatin and induces accessibility by recruiting the BRG1 chromatin remodeler subunit. However, it remains unclear whether the function of EBF1 is continuously required for stabilizing local chromatin accessibility. To this end, we replaced EBF1 by EBF1-FKBP F36V in pro-B cells, allowing the rapid degradation by adding the degradation TAG13 (dTAG13) dimerizer. EBF1 degradation results in a loss of genome-wide EBF1 occupancy and EBF1-targeted BRG1 binding. Chromatin accessibility was rapidly diminished at EBF1-binding sites with a preference for sites whose occupancy requires the pioneering activity of the C-terminal domain of EBF1. Diminished chromatin accessibility correlated with altered gene expression. Thus, continuous activity of EBF1 is required for the stable maintenance of the transcriptional and epigenetic state of pro-B cells.

中文翻译：

---

EBF1 持续需要稳定 pro-B 细胞中的局部染色质可及性

在淋巴祖细胞中建立从头染色质可及性需要转录因子 (TF) 早期 B 细胞因子 1 (EBF1) 的“先驱”功能，它与幼稚染色质结合并通过募集 BRG1 染色质重塑子亚基诱导可及性。然而，目前尚不清楚 EBF1 的功能是否是稳定局部染色质可及性所必需的。为此，我们将 EBF1 替换为 EBF1-FKBPF36V在 pro-B 细胞中，通过添加降解 TAG13 (dTAG13) 二聚化剂允许快速降解。EBF1 降解导致全基因组 EBF1 占用和 EBF1 靶向 BRG1 结合的丧失。EBF1 结合位点的染色质可及性迅速降低，优先选择需要 EBF1 C 末端域先驱活动的位点。染色质可及性降低与基因表达改变相关。因此，稳定维持 pro-B 细胞的转录和表观遗传状态需要 EBF1 的持续活性。