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Epigenetic Regulation of Myeloid Cells

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  • Authors: Lionel B. Ivashkiv1, Sung Ho Park3
  • Editor: Siamon Gordon4
    Affiliations: 1: Arthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Center, Hospital for Special Surgery, New York, NY 10021; 2: Department of Medicine and Immunology and Microbial Pathogenesis Program, Weill Cornell Medical College, New York, NY 10021; 3: Arthritis and Tissue Degeneration Program and David Z. Rosensweig Genomics Center, Hospital for Special Surgery, New York, NY 10021; 4: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0010-2015
  • Received 13 May 2015 Accepted 30 September 2015 Published 03 June 2016
  • Lionel B. Ivashkiv, [email protected]
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  • Abstract:

    Epigenetic regulation in myeloid cells is crucial for cell differentiation and activation in response to developmental and environmental cues. Epigenetic control involves posttranslational modification of DNA or chromatin, and is also coupled to upstream signaling pathways and transcription factors. In this review, we summarize key epigenetic events and how dynamics in the epigenetic landscape of myeloid cells shape the development, immune activation, and innate immune memory.

  • Citation: Ivashkiv L, Park S. 2016. Epigenetic Regulation of Myeloid Cells. Microbiol Spectrum 4(3):MCHD-0010-2015. doi:10.1128/microbiolspec.MCHD-0010-2015.

Key Concept Ranking

Transcription Start Site
Innate Immune System
Tumor Necrosis Factor
Gene Expression
Interferon Regulatory Factors


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Epigenetic regulation in myeloid cells is crucial for cell differentiation and activation in response to developmental and environmental cues. Epigenetic control involves posttranslational modification of DNA or chromatin, and is also coupled to upstream signaling pathways and transcription factors. In this review, we summarize key epigenetic events and how dynamics in the epigenetic landscape of myeloid cells shape the development, immune activation, and innate immune memory.

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Epigenetic features of promoters and enhancers of inflammatory genes under basal and acute activated conditions. During macrophage differentiation, PU.1 binds to promoters and enhancers and facilitates the opening of chromatin and an increase in H3K4me3 at promoters and H3K4me1 at enhancers. The negative histone marks/corepressors also are distributed at both promoters and enhancers. There is often low or nonproductive basal transcription. Inflammatory stimulation of macrophages leads to release and loss of corepressors and negative histone marks, increased histone acetylation, additional nucleosome remodeling by BRG1, and recruitment of signaling transcription factors such as NF-κB. The subsequent recruitment of histone acetyltransferases (HATs) results in histone acetylation, which is subsequently bound by Brd4/P-TEFb complex. This results in successive rounds of Pol II elongation and active transcription. Enhancers of active genes are characterized by occupancy by HATs, H3K27ac, and low levels of transcription of eRNA. Interaction between enhancers and promoters involves structural connections that include the Mediator complex and cohesions to promote formation of the preinitiation complex, to initiate transcription. Substantial data support that many interactions between enhancers and promoters (“looping”) are constitutive, although it is possible that such interactions may be enhanced by stimulation. NFR, nucleosome free region.

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0010-2015
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Epigenetic regulators of macrophage polarization. A color spectrum illustrates different polarized macrophage populations, showing the linear scale of two macrophage designations, M1 and M2. Histone modifiers implicated in M1 and M2 macrophage polarization are indicated. TF, transcription factor.

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0010-2015
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Epigenetic regulation of endotoxin tolerance and trained immunity in macrophages. A proposed model of endotoxin tolerance and trained immunity is depicted in the graph. The red line indicates tolerized genes that remain refractory to a second stimulus, and the blue line represents trained genes that show enhanced expression in response to subsequent stimulation. Innate immune responses during and after first stimuli can lead to epigenetic reprogramming, which translates into decreased or increased immune response to subsequent stimulation.

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0010-2015
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