Tissue-resident Macrophage Enhancer Landscapes Are Shaped by the Local Microenvironment

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2014 Dec 7

PMID 25480296

Citations 1083

Authors

Yonit Lavin

Deborah Winter

Ronnie Blecher-Gonen

Eyal David

Hadas Keren-Shaul

Miriam Merad

Steffen Jung

Ido Amit

Affiliations

Soon will be listed here.

Abstract

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 reprogrammed when transferred into a new microenvironment. These results provide a comprehensive view of macrophage regulatory landscape and highlight the importance of the microenvironment, along with pioneer factors in orchestrating identity and plasticity.

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