EPIGENETIC MECHANISMS INVOLVED DURING ENCYSTATION AND ANTIGENIC VARIATION IN Giardia lamblia

CARRANZA PG, PRUCCA CG, TORRI A, SAURA A, LUJÁN HD; CESAR G PRUCCA; ALESSANDRO TORRI; ALICIA SAURA; HUGO D LUJAN

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

Giardia lamblia is one of the most common causes of intestinal disease in humans. To adapt to different environments both outside and inside of the host?s small intestine, this early-branching eukaryote undergoes the adaptive processes of differentiation into cyst and antigenic variation, respectively. In this work, we studied if epigenetic factors, like histone modifications, are involved in both processes. Giardia lacks canonical histone H1 but possesses the core histones H2a, H2b, H3 and H4, which form the nucleosone where the DNA is wrapped. Using specific antibodies against histone modifications and chromatin inmunoprecipitation assays (CHIP), we determined the dynamics of different histone marks during encystation and antigenic variation. When Giardia clones were exposed to specific inhibitors of histone deacetylase enzymes, inhibition of encystation and a significant increase on the switching rate of surface antigens (VSPs) was observed. We also identified and characterized all Giardia histone deacetylase enzymes from the genome of the parasite, which can be separated in non-NAD+- dependent (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 human parasite.