Putative SET-domain methyltransferases in Cryptosporidium parvum and histone methylation during infection

Manasi Sawant1, Sadia Benamrouz-Vanneste1,2, Dionigia Meloni1

  • 1Université de Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Centre d'Infection et d'Immunité de Lille, Lille, France.

Virulence
|September 13, 2022
PubMed

Insights

This study reveals that Cryptosporidium parvum alters host epigenetic regulation by decreasing histone methylation. Understanding these epigenetic changes in the parasite and host may lead to new infection control strategies.

Area of Science:

  • Epigenetics
  • Parasitology
  • Molecular Biology

Background:

  • Cryptosporidium parvum causes widespread diarrheal illness, particularly in vulnerable populations.
  • The parasite's pathogenic mechanisms and impact on host gene expression remain poorly understood.
  • Recent links between C. parvum and oncogenesis highlight the need to investigate its effects on host genome regulation.

Purpose of the Study:

  • To investigate histone lysine methylation during the C. parvum life cycle.
  • To identify and characterize lysine methyltransferases (KMTs) in C. parvum.
  • To examine the impact of C. parvum infection on host histone lysine methylation patterns.

Main Methods:

  • Phylogenetic and structural analysis of SET-domain containing proteins in C. parvum.
  • Analysis of CpSET gene expression throughout the parasite life cycle.
  • Detection of specific histone lysine methylation marks using methyl-lysine antibodies.
  • Assessment of host histone methylation levels (H3K36me3, H3K27me3) following C. parvum infection.

Main Results:

  • Identification and classification of C. parvum KMTs into distinct subfamilies (CpSET1, CpSET2, CpSET8, CpKMTox, CpAKMT).
  • Characterization of CpSET1, CpSET2, and CpSET8 as histone lysine methyltransferases (HKMTs).
  • Dynamic changes in parasite histone methylation (H3K4me, H3K36me, H4K20me) observed during the parasite life cycle.
  • Significant decrease in host H3K36me3 and H3K27me3 levels upon C. parvum infection.

Conclusions:

  • This study provides the first description of epigenetic mechanisms in C. parvum throughout its life cycle and during host-parasite interaction.
  • C. parvum possesses functional HKMTs involved in dynamic histone methylation.
  • The parasite actively manipulates host epigenetic regulation, evidenced by reduced host H3K36me3 and H3K27me3.
  • Understanding these epigenetic interactions may reveal novel strategies for controlling Cryptosporidium infections.

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