Goode Debbie K, Obier Nadine, Vijayabaskar M S, Lie-A-Ling Michael, Lilly Andrew J, Hannah Rebecca, Lichtinger Monika, Batta Kiran, Florkowska Magdalena, Patel Rahima, Challinor Mairi, Wallace Kirstie, Gilmour Jane, Assi Salam A, Cauchy Pierre, Hoogenkamp Maarten, Westhead David R, Lacaud Georges, Kouskoff Valerie, Göttgens Berthold, Bonifer Constanze
Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust and MRC Cambridge Stem Cell Institute, Cambridge CB2 0XY, UK.
Institute of Cancer end Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B152TT, UK.
Dev Cell. 2016 Mar 7;36(5):572-87. doi: 10.1016/j.devcel.2016.01.024. Epub 2016 Feb 25.
Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development.
后生动物的发育涉及特定基因表达程序的相继激活和沉默，由组织特异性转录因子驱动，这些因子塑造染色质景观。为了理解这一过程如何执行整个发育途径，我们从纯化的胚胎干细胞衍生细胞中生成了全局基因表达、染色质可及性、组蛋白修饰和转录因子结合数据，这些细胞代表造血特化和分化的六个连续阶段。我们的数据揭示了驱动差异基因表达的调控元件的性质，并说明了转录因子结合如何影响启动子活性。我们提出了一个用于造血特化的动态核心调控网络模型，并证明了其在重编程实验设计中的实用性。基于我们全基因组数据的功能研究揭示了TEAD/YAP因子在哺乳动物造血特化中的阶段特异性作用。我们的研究为研究造血作用提供了一个强大的资源，并展示了这些数据如何增进我们对哺乳动物发育的理解。
