Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment.
Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment.
复制标题
DOI：
10.1016/j.cell.2014.11.018
复制
发表时间：
2014-12-04
期刊：
影响因子：
64.5
通讯作者：
Amit I
中科院分区：
文献类型：
--
作者：
Lavin Y;Winter D;Blecher-Gonen R;David E;Keren-Shaul H;Merad M;Jung S;Amit I
巨噬细胞对先天免疫防御至关重要，并且还以组织特异性方式控制器官稳态。他们提供了一个合适的模型来研究个体发育和微环境对染色质状态的影响，以及染色质修饰是否有助于巨噬细胞的身份。在这里，我们分析了七个组织驻留巨噬细胞群体中四种组蛋白修饰的动态。我们确定了12，743个巨噬细胞特异性增强子，并确定组织驻留巨噬细胞具有独特的增强子景观，超出了发育起源的解释。结合我们的增强子目录与基因表达谱和开放的染色质区域，我们表明，组织和谱系特异性转录因子的组合形成的调控网络控制染色质规格在组织驻留的巨噬细胞。环境能够塑造移植骨髓前体的染色质景观，甚至分化的巨噬细胞在转移到新的微环境中时也可以重新编程。这些结果提供了巨噬细胞调控景观的全面视图，并突出了微环境的重要性，沿着先驱因素在协调身份和可塑性。
Macrophages are critical for innate immune defense and also control organ homeostasis in a tissue-specific manner. They provide a fitting model to study the impact of ontogeny and microenvironment on chromatin state and whether chromatin modifications contribute to macrophage identity. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes beyond what can be explained by developmental origin. Combining our enhancer catalog with gene expression profiles and open chromatin regions, we show that a combination of tissue- and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment is capable of shaping the chromatin landscape of transplanted bone marrow precursors, and even differentiated macrophages can be reprogramed when transferred into a new microenvironment. These results provide a comprehensive view of macrophage regulatory landscape and highlight the importance of the micro-environment, along with pioneer factors in orchestrating identity and plasticity.
登录
查看更多内容
影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
64.5
作者：
Haldar M;Kohyama M;So AY;Kc W;Wu X;Briseño CG;Satpathy AT;Kretzer NM;Arase H;Rajasekaran NS;Wang L;Egawa T;Igarashi K;Baltimore D;Murphy TL;Murphy KM
通讯作者：
Murphy KM
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.8
作者：
Felsenfeld, G;Groudine, M
通讯作者：
Groudine, M