A network of epigenetic regulators guides developmental haematopoiesis in vivo.
A network of epigenetic regulators guides developmental haematopoiesis in vivo.
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DOI：
10.1038/ncb2870
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发表时间：
2013-12
影响因子：
21.3
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中科院分区：
文献类型：
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细胞程序的启动是由激活或抑制靶基因表达的关键转录因子和染色质调节因子精心策划的。为了获得在发育造血过程中建立表观遗传密码的染色质因子纲要，对斑马鱼中425个人类染色质因子的同源物进行了大规模的反向遗传筛选。一组染色质调节因子被确定针对原始和最终血液形成的不同阶段，包括以前未涉及造血的因素。我们确定了15个调节原始红系祖细胞发育的因子和29个调节终代干细胞和祖细胞发育的因子。这些染色质因子与SWI/SNF和ISWI染色质重塑、SET1甲基转移酶、CBP/P300/HBO1/NuA4乙酰转移酶、HDAC/NuRD去乙酰化酶和Polycomb抑制复合物有关。我们的工作提供了一个全面的观点，即特定的染色质因子及其相关复合物如何在体内造血细胞的建立中发挥重要作用。
The initiation of cellular programs is orchestrated by key transcription factors and chromatin regulators that activate or inhibit target gene expression. To generate a compendium of chromatin factors that establish the epigenetic code during developmental hematopoiesis, a large-scale reverse genetic screen was conducted targeting orthologs of 425 human chromatin factors in zebrafish. A set of chromatin regulators was identified that target different stages of primitive and definitive blood formation, including factors not previously implicated in hematopoiesis. We identified 15 factors that regulate development of primitive erythroid progenitors and 29 factors that regulate development of definitive stem and progenitor cells. These chromatin factors are associated with SWI/SNF and ISWI chromatin remodeling, SET1 methyltransferase, CBP/P300/HBO1/NuA4 acetyltransferase, HDAC/NuRD deacetylase, and Polycomb repressive complexes. Our work provides a comprehensive view of how specific chromatin factors and their associated complexes play a major role in the establishment of hematopoietic cells in vivo.