Epigenetic mechanisms involveed during encystation and antigenic variation in Giardia lamblia

CARRANZA PG; PRUCCA CG; TORRI A; SAURA A; LUJAN HD

Puerto Madryn

Congreso; XLVI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Giardia lamblia is one of the most common causes of intestinal disease in humans. To adapt to differente environments both outside and inside of the host´s small intestine, this early-branching eukaryote undergoes the adaptative processes of differentiation into cyst and antigenic variation, respectively. In this work, we studied if epigenetic factors, like histone modifrfications, are involved in both processes. Giardia lacks canonical histone H1 but processesses the core histone H2a, H2b, H3 y H4, which form the nucleosome where the DNA is wrapped. Using specific antibodies against histones modifications and chromatin inmunoprecipitation assays (CHIP), we determined the dynamics of different histone marks during encystations and antigenic variation. When Giardia clones were exposed to specific inhibitors of histones deacetylase enzymes, inhibition of encystations and a significant increase of the switching rate of surface antigens (VSPs) was observed. We also identified all Giardia histone deacetylase encymes from the genome of the parasite, which can be separated into non-NAD+-dependant (HDACs) and NAD+-dependent. Our results indicated that several histone modifications, in particular acetylation of lysines in Giardia histone H3 and H4 are directly involved in controlling adaptation and differentiation of this important parasite.