Chromatin reader Dido3 regulates the genetic network of B cell differentiation

The development of hematopoietic lineages is based on a complex balance of transcription factors whose expression depends on the epigenetic signatures that characterize each differentiation step. The B cell lineage arises from hematopoietic stem cells through the stepwise silencing of stemness genes and balanced expression of mutually regulated transcription factors, as well as DNA rearrangement. Here we report the impact on B cell differentiation of lack of Dido3, a reader of the chromatin status, in the hematopoietic compartment. We found a reduced DNA accessibility in hematopoietic precursors, leading to severe deficiency in the generation of successive B cell differentiation stages. The expression of essential transcription factors and differentiation markers is affected, as is the somatic recombination process. List of chromatin accessibility regions and mRNA profiles of DIDO3 wild type and mutants in mouse hematopoietic precursors

造血谱系（hematopoietic lineages）的发育基于转录因子（transcription factors）的复杂平衡体系，此类转录因子的表达取决于各分化阶段特有的表观遗传标记（epigenetic signatures）。B细胞谱系（B cell lineage）由造血干细胞（hematopoietic stem cells）通过逐步沉默干细胞干性基因、平衡表达相互调控的转录因子以及DNA重排（DNA rearrangement）过程产生。我们在此报道染色质状态阅读器（chromatin reader）Dido3在造血区室（hematopoietic compartment）中缺失对B细胞分化的影响：研究发现造血前体细胞（hematopoietic precursors）的DNA可及性（DNA accessibility）显著降低，导致连续B细胞分化各阶段的生成出现严重缺陷，核心转录因子与分化标志物的表达以及体细胞重排（somatic recombination）过程均受到干扰。本数据集包含小鼠造血前体细胞中DIDO3野生型与突变体的染色质可及性区域列表及mRNA表达谱（mRNA profiles）。