The histone methylase KMTox interacts with the redox-sensor peroxiredoxin-1 and targets genes involved in Toxoplasma gondii antioxidant defences.
The ability of living cells to alter their gene expression patterns in response to environmental changes is essential for viability. Oxidative stress represents a common threat for all aerobic life. In normally growing cells, in which hydrogen peroxide generation is transient or pulsed, the antioxidant systems efficiently control its concentration. Intracellular parasites must also protect themselves against the oxidative burst imposed by the host. In this work, we have investigated the role of KMTox, a new histone lysine methyltransferase, in the obligate intracellular parasite Toxoplasma gondii. KMTox is a nuclear protein that holds a High Mobility Group domain, which is thought to recognize bent DNA. The enzyme methylates both histones H4 and H2A in vitro with a great preference for the substrate in reduced conditions. Importantly, KMTox interacts specifically with the typical 2-cys peroxiredoxin-1 and the binding is to some extent enhanced upon oxidation. It appears that the cellular functions that are primarily regulated by the KMTox are antioxidant defences and maintenance of cellular homeostasis. KMTox may regulate gene expression in T. gondii by providing the rapid re-arrangement of chromatin domains and by interacting with the redox-sensor TgPrx1 contribute to establish the antioxidant 'firewall' in T. gondii.
Sautel
Céline F
CF
Laboratoire Adaptation et Pathogénie des Micro-organismes, Université Joseph Fourier GRENOBLE 1, BP 170, F-38042 Grenoble cedex 9, France.
Ortet
Philippe
P
Saksouk
Nehmé
N
Kieffer
Sylvie
S
Garin
Jérôme
J
Bastien
Olivier
O
Hakimi
Mohamed-Ali
MA
D000818:Animals; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D016053:RNA, Protozoan / Q000235:genetics; D014122:Toxoplasma / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics
D006657:Histones; D015800:Protozoan Proteins; D016053:RNA, Protozoan; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D011495:Histone-Lysine N-Methyltransferase