The unfavorable clinical outcome of COVID-19 in smokers is mediated by H3K4me3, H3K9me3 and H3K27me3 histone marks

Epigenomics. 2022 Feb;14(3):153-162. doi: 10.2217/epi-2021-0476. Epub 2022 Jan 13.

Abstract

Smoking could predispose individuals to a more severe COVID-19 by upregulating a particular gene known as mdig, which is mediated through a number of well-known histone modifications. Smoking might regulate the transcription-activating H3K4me3 mark, along with the transcription-repressing H3K9me3 and H3K27me3 marks, in a way to favor SARS-CoV-2 entry by enhancing the expression of ACE2, NRP1 and NRP2, AT1R, CTSD and CTSL, PGE2 receptors 2-4, SLC6A20 and IL-6, all of which interact either directly or indirectly with important receptors, facilitating viral entry in COVID-19.

Keywords: COVID-19; H3K27me3; H3K4me3; HeK9me3; SARS-CoV-2; epigenetic gene regulation; epigenetics and disease; histone modifications; mdig; smoking.

Plain language summary

Lay abstract The role of smoking in development of several respiratory diseases has been clearly established. A significant proportion of these deleterious effects is mediated through epigenetic mechanisms, particularly histone modifications. Recent evidence indicates that smoking induces the expression of a mediator known as mdig, which in turn alters the transcription of several key proteins that have been implicated in development of COVID-19.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism
  • COVID-19 / diagnosis
  • COVID-19 / genetics*
  • COVID-19 / metabolism
  • COVID-19 / virology
  • Cathepsin D / genetics
  • Cathepsin D / metabolism
  • Cathepsin L / genetics
  • Cathepsin L / metabolism
  • Dioxygenases / genetics*
  • Dioxygenases / metabolism
  • Epigenesis, Genetic*
  • Histone Demethylases / genetics*
  • Histone Demethylases / metabolism
  • Histones / genetics*
  • Histones / metabolism
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Methylation
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism
  • Neuropilin-2 / genetics
  • Neuropilin-2 / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational*
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, Prostaglandin E / genetics
  • Receptors, Prostaglandin E / metabolism
  • Risk Factors
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / growth & development
  • SARS-CoV-2 / metabolism
  • Smoking / genetics*
  • Smoking / metabolism
  • Smoking / pathology
  • Virus Internalization

Substances

  • AGTR1 protein, human
  • Histones
  • IL6 protein, human
  • Interleukin-6
  • Membrane Transport Proteins
  • NRP1 protein, human
  • Neuropilin-2
  • Nuclear Proteins
  • Protein Isoforms
  • Receptor, Angiotensin, Type 1
  • Receptors, Prostaglandin E
  • SLC6A20 protein, human
  • histone H3 trimethyl Lys4
  • neuropilin-2, human
  • Neuropilin-1
  • Dioxygenases
  • Histone Demethylases
  • RIOX2 protein, human
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • CTSL protein, human
  • Cathepsin L
  • CTSD protein, human
  • Cathepsin D