Regulation of histone H3 lysine 9 methylation in inflammation

Abstract

Inflammation is a defense mechanism that the immune system uses in response to harmful stimuli such as pathogens, damaged cells, toxic compounds, or irradiation. These stimuli may induce inflammatory response and potentially tissue damage in respiratory, cardiovascular, digestive, nervous, endocrine, urinary, or reproductive systems. Inflammatory diseases include a broad array of disorders and conditions that are characterized by inflammation, ranging from autoimmune disease, atopic dermatitis, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, glomerulonephritis, hepatitis, reperfusion injury, transplant rejection, diabetes, cancer, Parkinson's disease, multiple sclerosis, to depression. Epigenetic mechanisms play crucial roles in many biological processes by regulating transcriptional activation or repression. Histone posttranslational modifications have emerged as prospective therapeutic targets. Methylation of histone 3 at lysine 9 is one of the most highly conserved epigenetic marks that correlate well with gene silencing. The methylation status of H3K9 modulates immune cell differentiation and immune responses and therefore influences the outcome of cancer, infection, and other inflammatory diseases. Here, we review the high impact and innovate discoveries in this field, highlight the critical role of the H3K9 methylation/de-methylation in human inflammatory diseases, discuss potential new therapeutic strategies based on a better understanding of the biology of H3K9 methylation modifications.

Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1

“…As previously mentioned, H3K9 methylation regulates multiple inflammatory pathways and therefore, we next tested directly whether NSP1 expression influenced H3K9 dimethylation [38,39]. ChIP-seq with specific anti-H3K9me2 antibodies yielded the expected pattern of chromatin modifications at genic loci (S2D Fig).…”

“…A recent study showed NSP1 interacting with PRRC2B [32], a poorly characterized protein that has been proposed to regulate translation, and also has been found to interact with EHMT2/ G9a [35][36][37]. G9a is a Histone H3 Lysine 9 (H3K9) mono-and di-methyl transferase setting repressive H3K9me and H3K9me2 marks that are known to regulate multiple inflammatory pathways [38][39][40][41][42]. Most importantly, PRRC2B along with the translation initiation factors eIF3a/eIF3G and Ribosomal Proteins RPS10/RPS10 are the only proteins among the strong interactants that lose affinity with the K164A/H165A in both C-terminal and N-terminal NSP1 tagging systems (S2A Fig) . This implies that any comparison of the WT vs K164A/ H165A may include a PRRC2B-mediatied effect.…”