Comprehensive Epigenomic Analysis Reveals Dynamic Regulatory Programs Of Blood Development (ChIP-seq)

Embryonic hematopoiesis is regulated by the coordinated interaction between transcription factors and the epigenetic regulators driving developmental-stage specific gene expression but how this process drives hematopoietic specification and terminal differentiation is poorly understood. Here we generated RNA-Seq, DNase-Seq and ChIP-Seq data for histone marks and transcription factors from ES-cell derived purified cells representing six sequential stages of blood cell specification and differentiation. Our data reveal the binding patterns of specific transcription factors involved in the priming and maintenance of distal elements and inform how binding impacts on promoter activity. Functional studies based on these data uncovered a previously unrecognised role for Hippo signalling in mammalian hematopoietic specification. Finally, we present a dynamic core regulatory network model for hematopoiesis and demonstrate its utility for the design of reprogramming experiments. Our study represents a powerful resource for studying hematopoiesis and demonstrates how such data can advance our understanding of mammalian development. ChIP-seq data of histone modifications and transcription factors, and RNA-seq data obtained from purified cells representing five sequential stages of murine blood cell specification and differentiation

胚胎造血（embryonic hematopoiesis）的调控依赖于转录因子（transcription factors）与表观遗传调控因子（epigenetic regulators）之间的协同互作，这类调控因子介导发育阶段特异性的基因表达程序，但目前学界对该过程如何推动造血谱系特化与终末分化的认知仍较为匮乏。本研究针对源自胚胎干细胞（ES cell）的纯化细胞群体，采集了覆盖造血谱系特化与分化六个连续阶段的样本，生成了针对组蛋白标记（histone marks）与转录因子的RNA测序（RNA-Seq）、DNase测序（DNase-Seq）及染色质免疫沉淀测序（ChIP-Seq）数据。本研究的数据揭示了参与远端调控元件（distal elements）预激活与维持的特定转录因子的结合模式，并阐明了此类结合如何影响启动子活性。基于该数据开展的功能研究还发现了Hippo信号通路（Hippo signalling）在哺乳动物造血谱系特化中此前未被报道的功能。最后，本研究构建了造血过程的动态核心调控网络模型，并验证了该模型可用于重编程实验（reprogramming experiments）的设计。本研究为造血领域的相关研究提供了极具价值的数据集资源，并阐明了此类组学数据如何推动我们对哺乳动物发育过程的认知。此外，本研究还提供了源自代表小鼠造血谱系特化与分化五个连续阶段的纯化细胞的组蛋白修饰与转录因子ChIP-Seq数据及RNA-Seq数据。