TY - JOUR
T1 - Integration of transcriptional and metabolic control in macrophage activation
AU - Natoli, Gioacchino
AU - Pileri, Francesco
AU - Gualdrini, Francesco
AU - Ghisletti, Serena
N1 - Funding Information:
The authors regret for being unable, due to length restriction, to cite all relevant studies and thank the reviewers for their helpful comments. The work related to the topic of this review in our laboratory is supported by the European Research Council (ERC grant 692789 MEDICI to G.N.) and Marie Sklodowska-Curie Actions (MSCA-IF ?MetChromTx? ID 789792 to F.G.). F.P. is a PhD student within the European School of Molecular Medicine (SEMM).
Funding Information:
The authors regret for being unable, due to length restriction, to cite all relevant studies and thank the reviewers for their helpful comments. The work related to the topic of this review in our laboratory is supported by the European Research Council (ERC grant 692789 MEDICI to G.N.) and Marie Sklodowska‐Curie Actions (MSCA‐IF “MetChromTx” ID 789792 to F.G.). F.P. is a PhD student within the European School of Molecular Medicine (SEMM).
Publisher Copyright:
© 2021 The Authors
PY - 2021/9/6
Y1 - 2021/9/6
N2 - Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus-specific changes in gene expression programs accompanied by extensive rewiring of metabolism, with alterations in chromatin modifications providing one layer of integration of transcriptional and metabolic regulation. A systematic and mechanistic understanding of the mutual influences between signal-induced metabolic changes and gene expression is still lacking. Here, we discuss current evidence, controversies, knowledge gaps, and future areas of investigation on how metabolic and transcriptional changes are dynamically integrated during macrophage activation. The cross-talk between metabolism and inflammatory gene expression is in part accounted for by alterations in the production, usage, and availability of metabolic intermediates that impact the macrophage epigenome. In addition, stimulus-inducible gene expression changes alter the production of inflammatory mediators, such as nitric oxide, that in turn modulate the activity of metabolic enzymes thus determining complex regulatory loops. Critical issues remain to be understood, notably whether and how metabolic rewiring can bring about gene-specific (as opposed to global) expression changes.
AB - Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus-specific changes in gene expression programs accompanied by extensive rewiring of metabolism, with alterations in chromatin modifications providing one layer of integration of transcriptional and metabolic regulation. A systematic and mechanistic understanding of the mutual influences between signal-induced metabolic changes and gene expression is still lacking. Here, we discuss current evidence, controversies, knowledge gaps, and future areas of investigation on how metabolic and transcriptional changes are dynamically integrated during macrophage activation. The cross-talk between metabolism and inflammatory gene expression is in part accounted for by alterations in the production, usage, and availability of metabolic intermediates that impact the macrophage epigenome. In addition, stimulus-inducible gene expression changes alter the production of inflammatory mediators, such as nitric oxide, that in turn modulate the activity of metabolic enzymes thus determining complex regulatory loops. Critical issues remain to be understood, notably whether and how metabolic rewiring can bring about gene-specific (as opposed to global) expression changes.
KW - epigenetics
KW - inflammation
KW - macrophages
KW - metabolism
KW - transcription
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U2 - 10.15252/embr.202153251
DO - 10.15252/embr.202153251
M3 - Review article
C2 - 34328708
AN - SCOPUS:85111644344
VL - 22
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 9
M1 - e53251
ER -