Sirtuin GdSir2.4 participates in the regulation of rRNA transcription in the Giardia duodenalis parasite

Mol Microbiol. 2021 May;115(5):1039-1053. doi: 10.1111/mmi.14710. Epub 2021 Mar 12.

Abstract

Giardia duodenalis is a parasite of great medical interest due to the number of infections it causes worldwide each year. Although research on epigenetic mechanisms in this protist has only begun recently, epigenetic regulation has already been shown to have important roles in encystation, antigenic variation, and resistance to antibiotics in Giardia. In this work, we show that a Giardia ortholog of Sir2, GdSir2.4, is involved in the silencing of rRNA expression. Our results demonstrate that GdSir2.4 localizes to the nucleolus, and its binding to the intergenic spacer region of the rDNA is associated with the deacetylation of the chromatin in this region. Given the importance of the regulation of rRNA expression to maintain adequate levels of ribosomes and genomic stability within the cells, GdSir2.4 can be considered a target to create new therapeutic agents against this parasite.

Keywords: ChIP; cell cycle; deacetylation; gene silencing; sirtuins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism
  • DNA, Ribosomal / genetics*
  • DNA, Ribosomal / metabolism
  • Epigenesis, Genetic
  • Gene Expression Regulation
  • Gene Silencing
  • Giardia lamblia / genetics
  • Giardia lamblia / metabolism*
  • Giardiasis / parasitology
  • Humans
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism*
  • RNA, Protozoan / genetics*
  • RNA, Protozoan / metabolism
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Transcription, Genetic*

Substances

  • Chromatin
  • DNA, Ribosomal
  • Protozoan Proteins
  • RNA, Protozoan
  • Sirtuins