HAT/HDAC: The epigenetic regulators of inflammatory gene expression (Review)

Swaroop,Surbhi; Batabyal,Anandi; Bhattacharjee,Ashish

doi:10.3892/ije.2021.5

HAT/HDAC: The epigenetic regulators of inflammatory gene expression (Review)

Authors:
- Surbhi Swaroop
- Anandi Batabyal
- Ashish Bhattacharjee
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Affiliations: Department of Biotechnology, National Institute of Technology, Durgapur, West Bengal 713209, India
Published online on: August 6, 2021 https://doi.org/10.3892/ije.2021.5
Article Number: 5
Copyright: © Swaroop et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inflammation is a condition through which the body responds to infection or tissue injury. It is typically characterized by the expression of a plethora of genes involved in inflammation, that are regulated by transcription factors, transcriptional co‑regulators, and chromatin remodeling events. Differential mitotically heritable patterns of gene expression without changes in the DNA sequence are essentially controlled by epigenetic regulation. Epigenetic mechanisms, such as histone modifications and DNA methylation have a profound effect on inflammatory gene transcription. Histone protein modifications, which include acetylation and the ubiquitination of lysine residues, the methylation of lysine and arginine, and the phosphorylation of serine have been found to modulate chromatin dynamics, thus altering the levels of gene expression. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate the addition and removal of acetyl groups from lysine residues on histones respectively. Nuclear factor (NF)‑κB, tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 are the pro‑inflammatory genes known to promote inflammatory responses in cells. By contrast, 15‑lipoxygenase‑1 (15‑LOX‑1) and monoamine oxidase‑A (MAO‑A) are the genes that can act against inflammation in certain specific conditions. 15‑LOX‑1, a lipid peroxidative enzyme, is associated with the development of inflammatory disorders, such as atherosclerosis, rheumatoid arthritis, asthma and renal injury. MAO‑A catalyzes degradation of biogenic amines and has been reported to cause oxidative stress, atherosclerosis and neuroinflammation. 15‑LOX‑1 has been shown to be co‑expressed along with MAO‑A, in both primary human monocytes and A549 lung carcinoma cells upon treatment with Th2 cytokines, such as IL‑4 and IL‑13. The present review aimed to discuss the HAT‑ and HDAC‑mediated epigenetic machinery which governs the expression of pro‑inflammatory genes, such as IL‑6, TNF‑α, etc., as well as the expression of anti‑inflammatory genes, such as 15‑LOX‑1 and MAO‑A, responsible for modulating the process of inflammation. On the whole, the present review aims to provide deeper insight into the underlying molecular mechanisms involved in the epigenetic regulation of inflammation, which may have novel implications in designing small molecule inhibitors that target the epigenetic machinery for the effective treatment of a variety of inflammation‑related diseases.

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