We Can Still Be Friends: IFN-γ Breaks Up Macrophage Enhancers Boris Novakovic, Cheng Wang, Colin Logie  Immunity  Volume 47, Issue 2, Pages 209-211 (August 2017) DOI: 10.1016/j.immuni.2017.08.002 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 IFN-γ-Mediated Gene Repression and Disassembly of Enhancers in Macrophages Freshly purified healthy human circulating monocytes were exposed to IFN-γ for 48 hr and subjected to genome-wide analyses, including RNA sequencing (RNA-seq), genome-wide histone 3 lysine 27 acetylation (H3K27ac ChIP-seq), chromatin accessibility (ATAC-seq), and transcription-factor chromatin immunoprecipitation (TF ChIP-seq). IFN-γ exposure specifically upregulated the expression of M1-phenotype genes and repressed M2-phenotype genes and their regulators. DNA-motif analysis of disassembled enhancers pointed to the transcription factor MAF, which was also repressed by IFN-γ. Loss or ectopic expression of MAF alone modulated IFN-γ downstream genes, and a IFN-γ signature is observed in rheumatoid arthritis synovial macrophages. Altogether, 12% of all enhancers that lost H3K27ac signal after IFNy exposure also lost the binding of lineage-determining transcription factors (LDTFs) and became closed. These are called disassembled enhancers (DEs). On the other hand, 16% of enhancers that gained H3K27ac signal also gained LDTF binding and open chromatin, corresponding to latent enhancers (LEs). Immunity 2017 47, 209-211DOI: (10.1016/j.immuni.2017.08.002) Copyright © 2017 Elsevier Inc. Terms and Conditions