The DNA-binding factor Ctcf critically controls gene expression in macrophages
The DNA-binding factor Ctcf critically controls gene expression in macrophages
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DOI：
10.1038/cmi.2013.41
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发表时间：
2014-01-01
影响因子：
24.1
通讯作者：
Hendriks, Rudi
中科院分区：
文献类型：
--
作者：
Nikolic, Tatjana;Movita, Dowty;Hendriks, Rudi
巨噬细胞在免疫和体内平衡中起重要作用。在通过特异性受体识别病原体后，它们迅速诱导炎症反应。这个过程在转录水平受到严格控制。DNA结合锌指蛋白CCCTC结合因子（Ctcf）是长距离染色质相互作用的关键调节因子，并协调转录因子和基因表达过程之间的特异性通信。本研究利用转基因Cre LoxP系统在骨髓细胞中特异性缺失Ctcf基因。在骨髓细胞中条件性缺失Ctcf基因在体内诱导了温和的表型。Ctcf缺陷小鼠表现出显着降低表达的主要组织相容性复合体（MHC）II类在肝脏中。ctcf缺陷的巨噬细胞表现出正常的表面表型和吞噬能力。在Toll样受体（TLR）刺激后，它们产生正常水平的促炎细胞因子IL-12和IL-6，但表现出产生肿瘤坏死因子（TNF）和IL-10以及表达IL-10家族成员IL-19、IL-20和IL-24的能力严重受损。总之，我们的数据表明，涉及微调巨噬细胞功能的Ctcf的作用。
Macrophages play an important role in immunity and homeostasis. Upon pathogen recognition via specific receptors, they rapidly induce inflammatory responses. This process is tightly controlled at the transcriptional level. The DNA binding zinc-finger protein CCCTC-binding factor (Ctcf) is a crucial regulator of long-range chromatin interactions and coordinates specific communication between transcription factors and gene expression processes. In this study, the Ctcf gene was specifically deleted in myeloid cells by making use of the transgenic Cre-LoxP system. Conditional deletion of the Ctcf gene in myeloid cells induced a mild phenotype in vivo. Ctcf-deficient mice exhibited significantly reduced expression of major histocompatibility complex (MHC) class II in the liver. Ctcf-deficient macrophages demonstrated a normal surface phenotype and phagocytosis capacity. Upon Toll-like receptor (TLR) stimulation, they produced normal levels of the pro-inflammatory cytokines IL-12 and IL-6, but manifested a strongly impaired capacity to produce tumor-necrosis factor (TNF) and IL-10, as well as to express the IL-10 family members IL-19, IL-20 and IL-24. Taken together, our data demonstrate a role of Ctcf that involves fine-tuning of macrophage function.