Epigenetic and chromatin profiling of wild-type and Dnmt3a-deficient B1 and B2 B cells. (RNA)

We have comprehensively interrogated wild type B1 and B2 B lineage cells and their progenitors. In mice bearing a conditional deletion of Dnmt3a in the B lineage, we integrated a variety of whole-genome profiling approaches including WGBS, TAB-Seq, RNA-seq, ATAC-Seq and CUT&RUN. The results reveal a stable "foundational methylome" in all B cells that establishes lymphocyte lineage identity. Superimposed on this foundational methylome is a "dynamic methylome" which is differentially modulated in B1 and B2 B cells by the coincident activity/recruitment of DNMT3A and TET enzymes. We compared the transcriptomes of wild-type and Dnmt3a-deficient B1 and B2 B cells.本研究全面解析了野生型B1、B2 B谱系细胞及其祖细胞。针对B谱系中存在DNA甲基转移酶3a (Dnmt3a) 条件性敲除的小鼠模型，我们整合了多种全基因组组学分析技术，包括全基因组亚硫酸氢盐测序 (Whole Genome Bisulfite Sequencing, WGBS)、TET辅助亚硫酸氢盐测序 (TET-Assisted Bisulfite Sequencing, TAB-Seq)、RNA测序 (RNA-seq)、转座酶可及性测序 (ATAC-Seq) 以及靶向切割与释放测序 (CUT&RUN)。研究结果揭示，所有B细胞中均存在稳定的"基础甲基化组"，该组学特征确立了淋巴细胞的谱系同一性；在此基础甲基化组之上，还存在一套"动态甲基化组"，其在B1与B2 B细胞中可通过DNMT3A与TET酶的协同活性/招募作用发生差异性调控。此外，我们还对比了野生型与Dnmt3a缺陷型B1、B2 B细胞的转录组。