Epigenetic Control of Macrophage Polarisation and Soluble Mediator Gene Expression during Inflammation

Figure 1

Epigenetic regulation in macrophages in homeostasis and inflammation. (a) During lineage establishment, the master macrophage regulator PU.1 unpacks the tight organisation of chromatin and binds to its motifs on the DNA sequence (arrows). Additional macrophage-restricted TFs interact with PU.1 and are subsequently recruited to the loosened DNA resulting in establishment of nucleosome-free regions at macrophage enhancers and promoters. (b) Enhancers are epigenetically marked by the H3K4me1 signature, whereas promoters are H3K4me3 labelled. Genes which are not active at baseline may be poised, meaning that their enhancers are marked by H3K27me3 signatures, rendering them ready to promote gene transcription in the presence of an appropriate stimulus. One category of such genes is the primary response genes, which exhibit active repression at their enhancers and are transcribed at low levels. (c) In the presence of local signals, these genes lose the suppressive H3K27me3 mark on their enhancers and promoters and are acetylated at H3K27 by the constitutively present p300 and recruited acetyltransferases. The produced transcripts are successfully elongated and leave the nucleus for protein synthesis. This conversion is facilitated by inflammation-related TF, which bring enhancers close to gene promoters to initiate gene transcription.

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