UMSBP2 is chromatin remodeler that functions in regulation of gene expression and suppression of antigenic variation in trypanosomes

Nucleic Acids Res. 2023 Jun 23;51(11):5678-5698. doi: 10.1093/nar/gkad402.

Abstract

Universal Minicircle Sequence binding proteins (UMSBPs) are CCHC-type zinc-finger proteins that bind the single-stranded G-rich UMS sequence, conserved at the replication origins of minicircles in the kinetoplast DNA, the mitochondrial genome of kinetoplastids. Trypanosoma brucei UMSBP2 has been recently shown to colocalize with telomeres and to play an essential role in chromosome end protection. Here we report that TbUMSBP2 decondenses in vitro DNA molecules, which were condensed by core histones H2B, H4 or linker histone H1. DNA decondensation is mediated via protein-protein interactions between TbUMSBP2 and these histones, independently of its previously described DNA binding activity. Silencing of the TbUMSBP2 gene resulted in a significant decrease in the disassembly of nucleosomes in T. brucei chromatin, a phenotype that could be reverted, by supplementing the knockdown cells with TbUMSBP2. Transcriptome analysis revealed that silencing of TbUMSBP2 affects the expression of multiple genes in T. brucei, with a most significant effect on the upregulation of the subtelomeric variant surface glycoproteins (VSG) genes, which mediate the antigenic variation in African trypanosomes. These observations suggest that UMSBP2 is a chromatin remodeling protein that functions in the regulation of gene expression and plays a role in the control of antigenic variation in T. brucei.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigenic Variation / genetics
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Gene Expression Regulation
  • Histones / genetics
  • Histones / metabolism
  • Protozoan Proteins* / metabolism
  • Telomere / genetics
  • Telomere / metabolism
  • Trypanosoma brucei brucei* / metabolism
  • Variant Surface Glycoproteins, Trypanosoma / genetics
  • Variant Surface Glycoproteins, Trypanosoma / metabolism

Substances

  • Chromatin
  • Histones
  • Variant Surface Glycoproteins, Trypanosoma
  • Protozoan Proteins