Monocytes and monocyte-derived macrophages originate through a multistep differentiation process. First, hematopoietic stem cells generate lineage-restricted progenitors that eventually develop into peripheral, postmitotic monocytes. Second, blood-circulating monocytes undergo differentiation into macrophages, which are specialized phagocytic cells capable of tissue infiltration. While monocytes mediate some level of inflammation and cell toxicity, macrophages boast the widest set of defense mechanisms against pathogens and elicit robust inflammatory responses. Here, we analyze the molecular determinants of monocytic and macrophagic commitment by profiling the EGR1 transcription factor. EGR1 is essential for monopoiesis and binds enhancers that regulate monocytic developmental genes such as CSF1R. However, differentiating macrophages present a very different EGR1 binding pattern. We identify novel binding sites of EGR1 at a large set of inflammatory enhancers, even in the absence of its binding motif. We show that EGR1 repressive activity results in suppression of inflammatory genes and is mediated by the NuRD corepressor complex.

单核细胞和单核细胞衍生的巨噬细胞起源于多步分化过程。首先，造血干细胞产生谱系受限的祖细胞，最终发育成外周的有丝分裂后单核细胞。其次，血液循环中的单核细胞分化为巨噬细胞，巨噬细胞是能够浸润组织的特化吞噬细胞。虽然单核细胞介导一定程度的炎症和细胞毒性，但巨噬细胞拥有最广泛的针对病原体的防御机制并引发强烈的炎症反应。在这里，我们通过分析 EGR1 转录因子来分析单核细胞和巨噬细胞承诺的分子决定因素。EGR1对于垄断和结合调节单核细胞发育基因（如CSF1R ）的增强子是必不可少的. 然而，分化的巨噬细胞呈现出非常不同的 EGR1 结合模式。我们在大量炎症增强剂中鉴定出 EGR1 的新结合位点，即使没有其结合基序。我们表明 EGR1 抑制活性导致炎症基因的抑制，并由 NuRD 辅助抑制因子复合物介导。