Genome-wide maps of chromatin state in HSC, Pro B and mature B cells

We have used a genome-wide ChIP-sequencing approach to define and investigate the dynamics of the cis-regulatory landscape in three developmental stages of the murine hematopoietic system. To this end, we have compared the profiles of H3K4me3, H3K4me1, H3K27ac, H3K27me3 and H3K9me2 in HSCs, committed pro-B and splenic mature B cells. We find the enhancer repertoire to be dynamically reshaped during hematopoiesis progression, surprisingly only a small fraction of primed enhancers in HSCs or committed progenitors become activated in subsequent stages. In turn, the majority of active enhancers in terminally differentiated cells are not primed in earlier stages. We also found that The heterochromatin mark H3K9me2 covers large domains that remain largely invariant across the three stages and are depleted in both active chromatin marks and the Polycomb related mark H3K27me3. Investigating enhancer dynamics in 3 different stages of B cell development本研究采用全基因组染色质免疫共沉淀测序（ChIP-sequencing）技术，对小鼠造血系统三个发育阶段的顺式调控景观动态特征进行了界定与探究。为此，我们对比了造血干细胞（hematopoietic stem cells, HSCs）、定型前B细胞以及脾脏成熟B细胞中H3K4me3、H3K4me1、H3K27ac、H3K27me3与H3K9me2的修饰图谱。研究发现，造血进程中增强子组库会发生动态重塑；令人意外的是，造血干细胞或定型祖细胞中仅极少数预激活增强子会在后续发育阶段被激活。与之相对，终末分化细胞中的绝大多数活性增强子并未在早期发育阶段完成预激活。我们还发现，异染色质标记H3K9me2所覆盖的大片基因组区域在三个发育阶段中基本保持恒定，且该区域同时缺乏活性染色质标记与多梳相关标记H3K27me3。本研究同时针对B细胞发育三个不同阶段的增强子动态变化展开了探究。