Role of histone modification on transcriptional regulation and HIV-1 gene expression: possible mechanisms of periodontal diseases in AIDS progression

Abstract

Although approximately 200 distinct cell types - including fibroblasts, neurons, and hematopoietic cells - possess the same DNA sequence, they have diverse functions in humans and exhibit considerably different gene expression patterns. It has become increasingly clear that epigenetic regulation plays an important role in gene expression. There are two major forms of epigenetic regulation: posttranslational modification of DNA-associated histone proteins in chromatin and methylation of DNA. These forms are regulated by distinct but coupled pathways. Notably, histone Lys acetylation by histone acetyltransferase and deacetylation by histone deacetylases play a crucial role in on-off regulation of gene expression. It is now understood that epigenetics plays an important role not only in the regulation of gene expression but also in the pathogenesis of a broad range of diseases such as cancer and microbial infections. We have determined that epigenetic regulation is involved in the establishment and maintenance of HIV-1 latency and in the reactivation of HIV-1 by periodontopathic bacteria. In this review, we focus on the effect of histone modification on transcriptional regulation and the contribution thereof to the regulation of HIV-1 gene expression during the lytic and latent stages of HIV-1 infection. Likewise, we discuss the mechanisms by which periodontal diseases may accelerate AIDS progression in infected individuals as a new systemic disease caused by periodontitis and describe potential therapeutic interventions based on epigenetic mechanisms.

Poly(ADP-Ribose) Polymerase 1 Promotes Transcriptional Repression of Integrated Retroviruses

“…DNA methyl transferase 1 methylates cytosine residues in the DNA that attract DNA methyl-binding proteins, which in turn recruit histone deacetylases. These enzymes remove acetyl groups from the tails of histones, causing chromatin condensation that results in repression of gene transcription (65)(66)(67)(68)(69).…”

Epigenetic Metabolite Acetate Inhibits Class I/II Histone Deacetylases, Promotes Histone Acetylation, and Increases HIV-1 Integration in CD4+T Cells

“…Resulting from the fermentation of indigestible food components by anaerobic commensal bacteria composing the gut microbiome (8-10, 14, 17, 19-24), SCFAs have been suggested to affect HIV-1-mediated disease progression (1)(2)(3)(4)(5)(6)(7)42). Previous studies have focused on the impact of the SCFA butyrate on reactivation of the provirus in cells latently infected with HIV-1.…”

“…Previous studies have focused on the impact of the SCFA butyrate on reactivation of the provirus in cells latently infected with HIV-1. It has been suggested that butyrate acts as an inhibitor of class I HDACs, leading to histone hyperacetylation and enhancement of HIV-1 gene transcription (2,3). Indeed, several lines of evidence indicate that HDACs in the total CD4 ϩ T cell population was evaluated by flow cytometry.…”

The Contribution of Next Generation Sequencing Technologies to Epigenome Research of Stem Cell and Tumorigenesis

“…The contributing enzymes on methylation and acetylation specifically affect toward various histone proteins [55]. As the switch in on-off regulation of gene expression, lysine residues acetylation on histones is associated with gene activation, whereas methylation of lysine residues can result in either activation or silencing on gene expressions [56]. As an epigenetic mechanism, posttranslational modifications of histones are involved in the regulation of normal and disease-associated development.…”