Transcriptional repression in macrophages—basic mechanisms and alterations in metabolic inflammatory diseases

Treuter, Eckardt; Fan, Rongrong; Huang, Zhiqiang; Jakobsson, Tomas; Venteclef, Nicolas

doi:10.1002/1873-3468.12850

Cited by 33 publications

(49 citation statements)

References 100 publications

(176 reference statements)

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“…Cholesterol efflux represents a major mechanism of macrophage cholesterol removal and recycling. ABCA1 and ABCG1 are major macrophage cholesterol transporters involved in cholesterol efflux, both are tightly regulated through TFs and coregulators (1,4,18,25). In this study, we discover a novel mechanism of endotoxin-induced Abca1 expression and cholesterol efflux by the coregulator GPS2 which seems conserved in both mouse and human macrophages.…”

Section: Discussionmentioning

confidence: 79%

“…Dissecting these complicated intrinsic connections between gene-specific chromatin structure, TF and coregulator composition remains a challenging task and goes beyond the resolution of today's applied experimental approaches. [For further discussion, see our review (25). ]…”

Section: Discussionmentioning

confidence: 99%

“…Our previous work had demonstrated that GPS2 cooperates with other subunits of the HDAC3 corepressor complex to repress transcription of inflammatory genes (25), but whether the complex is involved in GPS2-dependent activation of Abca1 remained to be clarified. We therefore used published ChIP-seq data to analyze the corepressor complex cistrome (i.e., genome-wide chromatin-binding patterns of individual subunits) at the Abca1 gene locus in BMDMs (26).…”

Section: Function Of Gps2-associated Corepressor Complex Subunits In mentioning

confidence: 99%

“…G protein pathway suppressor 2 (GPS2) is an epigenome modulator involved in inflammatory gene regulation that acts in many contexts as a core subunit of a fundamental chromatin-modifying corepressor complex containing histone deacetylase 3 (HDAC3), NCOR, and silencing mediator of retinoid and thyroid receptors (SMRT, also NCOR2) (25). GPS2 interplays with TFs, such as c-Jun (26), and several lipid-sensing nuclear receptors (27)(28)(29)(30)(31).…”

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G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages

et al. 2018

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Macrophages play important roles in linking alterations of cholesterol metabolism and inflammation to the development of atherosclerosis. Previous studies have identified several positive and negative crosstalk mechanisms that connect cholesterol efflux and inflammation at the transcriptional level. Of particular relevance is that the expression of ATP‐binding cassette transporter A1 (Abca1), a main regulator of cholesterol efflux, can be induced by oxysterol receptor LXR agonists but also by bacterial endotoxins, such as LPS, that activate TLR4 signaling. However, the extent to which these pathways influence each other has remained incompletely understood. We investigated the possible role of the transcriptional coregulator G protein pathway suppressor 2 (GPS2) in LPS‐induced Abca1 expression and cholesterol efflux in mouse and human macrophages. To activate Abca1, GPS2 cooperates with the LPS‐inducible NF‐κB subunit p65, but not with LXRs nor with corepressor complex subunits that otherwise cooperate with GPS2 to repress proinflammatory gene expression. Overall, our work identifies a regulatory chromatin component of crosstalk mechanisms between cholesterol efflux and inflammation that specifically affects ABCA1. Because GPS2 expression is down‐regulated in some humans with obese and type 2 diabetes, the macrophage GPS‐2/ABC‐A1 pathway could be altered and contribute to atherogenesis.—Huang, Z., Liang, N., Damdimopoulos, A., Fan, R., Treuter, E. G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages. FASEB J. 33, 1631–1643 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Function Of Gps2-associated Corepressor Complex Subunits In mentioning

confidence: 99%

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confidence: 99%

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G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages

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“…Their immunophenotype and effector functions are determined by the tissue milieu they reside in, and influenced by metabolic processes. On the one hand, we have reviews dissecting the basic molecular or metabolic processes at work in macrophages such as transcriptional repression , nuclear receptor action , and the effect of the Krebs cycle . On the other, we present reviews looking at the interaction of metabolism and macrophage biology in physiological and pathological processes such as normal skeletal muscle regeneration , tumor progression , and atherosclerosis .…”

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confidence: 99%

Immunity meets metabolism and then they start talking

Nagy

Ellmeier

2017

FEBS Letters

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A narrow focus and ignorance of other fields or biological processes is a common danger in scientific research. This reductionist approach is useful to understand molecular or even atomic details of processes, but fails to provide answers to complex biological questions and diseases.Two major fields of research, immunity and metabolism, have been developing largely isolated from each other until recent years. These disciplines have been traditionally residing in different university departments and taught from different textbooks with little or no cross references.However, key advances have linked these areas inseparably by now, and allowed researchers solely focused on immunological problems to address issues related to chronic metabolic diseases, and scientists interested in the intricacies of metabolic regulation to work on unresolved puzzles of the immune system. The cross fertilization of immunology by metabolism, and metabolism by inflammation and immunity, tremendously broadened our horizon and provided new testable models and hypotheses regarding the origin and progression of metabolic diseases such as morbid obesity, diabetes, atherosclerosis, and cardiovascular disease. Similarly, the unraveling of metabolic processes underpinning or governing immune cell activation, differentiation into effector cells, and regulation of their function, holds promise to influence chronic inflammatory diseases as well as tumor growth and progression.In this Special Issue, we cannot cover all the interesting advances and developments of this emerging field; rather, we chose to focus on selected areas.One of the foci of this issue is macrophage biology. Macrophages are versatile, multitasking and very plastic components of the innate immune system. One can look at them as the Swiss Army Knife of the body. They are present in virtually every tissue and can also be recruited to all parts of the body during inflammation. Their immunophenotype and effector functions are determined by the tissue milieu they reside in, and influenced by metabolic processes. On the one hand, we have reviews dissecting the basic molecular or metabolic processes at work in macrophages such as transcriptional repression [1], nuclear receptor action [2], and the effect of the Krebs cycle [3]. On the other, we present reviews looking at the interaction of metabolism and macrophage biology in physiological and pathological processes such as normal skeletal muscle regeneration [4], tumor progression [5], and atherosclerosis [6]. Along these lines, Desvergne and colleagues discuss the concept of metaflammation, and the pathological interaction of metabolism and inflammation in the liver and the adipose tissue [7].Another hot topic is the regulation of T-cell activation and T-cell effector differentiation. A close-up on the role of the mTORC signaling pathway in innate and adaptive immune cell regulation and function is presented by Weichhart and colleagues [8]. In addition, we have reviews analyzing how metabolic pathways govern T-cell function [9], as ...

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Transcriptional repression shapes the identity and function of tissue macrophages

2021

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The changing extra‐ and intracellular microenvironment calls for rapid cell fate decisions that are precisely and primarily regulated at the transcriptional level. The cellular components of the immune system are excellent examples of how cells respond and adapt to different environmental stimuli. Innate immune cells such as macrophages are able to modulate their transcriptional programs and epigenetic regulatory networks through activation and repression of particular genes, allowing them to quickly respond to a rapidly changing environment. Tissue macrophages are essential components of different immune‐ and nonimmune cell‐mediated physiological mechanisms in mammals and are widely used models for investigating transcriptional regulatory mechanisms. Therefore, it is critical to unravel the distinct sets of transcription activators, repressors, and coregulators that play roles in determining tissue macrophage identity and functions during homeostasis, as well as in diseases affecting large human populations, such as metabolic syndromes, immune‐deficiencies, and tumor development. In this review, we will focus on transcriptional repressors that play roles in tissue macrophage development and function under physiological conditions.

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Transcriptional repression in macrophages—basic mechanisms and alterations in metabolic inflammatory diseases

Cited by 33 publications

References 100 publications

G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages

G protein pathway suppressor 2 (GPS2) links inflammation and cholesterol efflux by controlling lipopolysaccharide‐induced ATP‐binding cassette transporter A1 expression in macrophages

Immunity meets metabolism and then they start talking

Transcriptional repression shapes the identity and function of tissue macrophages

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