Environment drives selection and function of enhancers controlling tissue-specific macrophage identities.
Environment drives selection and function of enhancers controlling tissue-specific macrophage identities.
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DOI：
10.1016/j.cell.2014.11.023
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发表时间：
2014-12-04
期刊：
影响因子：
64.5
通讯作者：
Glass CK
中科院分区：
文献类型：
--
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
巨噬细胞基本上存在于身体的所有组织中，并在先天性和适应性免疫应答中发挥关键作用。不同的组织巨噬细胞群体也获得对正常组织稳态重要的特定功能。为了研究负责组织特异性功能的机制，我们分析了脑小胶质细胞和腹膜腔驻留巨噬细胞的转录组和增强子景观。此外，我们利用天然遗传变异作为全基因组“诱变”策略，以识别促进巨噬细胞谱系决定因子PU.1的共同或亚群特异性结合的转录因子的DNA识别基序。我们发现，不同的组织环境驱动不同的程序的基因表达的差异激活一个共同的增强子库，并通过诱导表达不同的二级转录因子，与PU.1建立组织特异性增强子。这些发现提供了对组织环境影响巨噬细胞表型的分子机制的见解，这些表型可能广泛适用于其他细胞类型。
Macrophages reside in essentially all tissues of the body and play key roles in innate and adaptive immune responses. Distinct populations of tissue macrophages also acquire context-specific functions that are important for normal tissue homeostasis. To investigate mechanisms responsible for tissue-specific functions, we analyzed the transcriptomes and enhancer landscapes of brain microglia and resident macrophages of the peritoneal cavity. In addition, we exploited natural genetic variation as a genome-wide ‘mutagenesis’ strategy to identify DNA recognition motifs for transcription factors that promote common or subset-specific binding of the macrophage lineage-determining factor PU.1. We find that distinct tissue environments drive divergent programs of gene expression by differentially activating a common enhancer repertoire and by inducing the expression of divergent secondary transcription factors that collaborate with PU.1 to establish tissue–specific enhancers. These findings provide insights into molecular mechanisms by which tissue environment influences macrophage phenotypes that are likely to be broadly applicable to other cell types.
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影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Mullen AC;Orlando DA;Newman JJ;Lovén J;Kumar RM;Bilodeau S;Reddy J;Guenther MG;DeKoter RP;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
10.5
作者：
Boudjelal, M;Taneja, R;Chambon, P
通讯作者：
Chambon, P