Department of Biological and Clinical Sciences, Linköping University, Linköping, Sweden.
Division of Molecular Hematology, Lund University, Lund, Sweden; and.
J Immunol. 2021 Jun 1;206(11):2700-2713. doi: 10.4049/jimmunol.2100048. Epub 2021 May 21.
B lymphocyte development is dependent on the interplay between the chromatin landscape and lineage-specific transcription factors. It has been suggested that B lineage commitment is associated with major changes in the nuclear chromatin environment, proposing a critical role for lineage-specific transcription factors in the formation of the epigenetic landscape. In this report, we have used chromosome conformation capture in combination with assay for transposase-accessible chromatin sequencing analysis to enable highly efficient annotation of both proximal and distal transcriptional control elements to genes activated in B lineage specification in mice. A large majority of these genes were annotated to at least one regulatory element with an accessible chromatin configuration in multipotent progenitors. Furthermore, the majority of binding sites for the key regulators of B lineage specification, EBF1 and PAX5, occurred in already accessible regions. EBF1 did, however, cause a dynamic change in assay for transposase-accessible chromatin accessibility and was critical for an increase in distal promoter-enhancer interactions. Our data unravel an extensive epigenetic priming at regulatory elements annotated to lineage-restricted genes and provide insight into the interplay between the epigenetic landscape and transcription factors in cell specification.
B 淋巴细胞的发育依赖于染色质景观和谱系特异性转录因子之间的相互作用。有人提出，B 细胞谱系的决定与核染色质环境的重大变化有关，这表明谱系特异性转录因子在形成表观遗传景观方面起着关键作用。在本报告中，我们使用染色质构象捕获结合转座酶可及染色质测序分析，以高效注释在小鼠 B 细胞谱系特化中激活的基因的近端和远端转录调控元件。这些基因中的绝大多数至少被注释到一个在多能祖细胞中具有可及染色质结构的调控元件。此外，B 细胞谱系特化的关键调节因子 EBF1 和 PAX5 的大多数结合位点都发生在已经可及的区域。然而，EBF1 确实导致了转座酶可及染色质可及性的动态变化，并且对于增加远端启动子-增强子相互作用至关重要。我们的数据揭示了注释为谱系受限基因的调控元件的广泛表观遗传启动，并深入了解细胞特化过程中表观遗传景观和转录因子之间的相互作用。
