title: Specific histone modifications play critical roles in the control of encystation and antigenic variation in the early-branching eukaryote Giardia lamblia.
abstract: During evolution, parasitic microorganisms have faced the challenges of adapting to different environments to colonize a variety of hosts. Giardia lamblia, a common cause of intestinal disease, has developed fascinating strategies to adapt both outside and inside its host's intestine, such as trophozoite differentiation into cyst and the switching of its major surface antigens. How gene expression is regulated during these adaptive processes remains undefined. Giardia lacks some typical eukaryotic features, like canonical transcription factors, linker histone H1, and complex promoter regions; suggesting that post-transcriptional and translational control of gene expression is essential for parasite survival. However, epigenetic factors may also play critical roles at the transcriptional level. Here, we describe the most common post-translational histone modifications; characterize enzymes involved in these reactions, and analyze their association with the Giardia's differentiation processes. We present evidence that NAD+-dependent and NAD+-independent histone deacetylases regulate encystation; however, a unique NAD+-independent histone deacetylase modulate antigenic switching. The rates of acetylation of H4K8 and H4K16 are critical for encystation, whereas a decrease in acetylation of H4K8 and methylation of H3K9 occur preferentially during antigenic variation. These results show the complexity of the mechanisms regulating gene expression in this minimalistic protozoan parasite.
authors: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Argentina.
authors: Pedro G
authors: PG
authors: Carranza
authors: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Argentina; Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
authors: Pablo R
authors: PR
authors: Gargantini
authors: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Argentina.
authors: César G
authors: CG
authors: Prucca
authors: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Argentina.
authors: Alessandro
authors: A
authors: Torri
authors: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Argentina; Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina.
authors: Alicia
authors: A
authors: Saura
authors: Department of Cell and Molecular Biology, Uppsala University, Sweden.
authors: Staffan
authors: S
authors: Svärd
authors: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Argentina; Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Córdoba, Argentina. Electronic address: hlujan@ucc.edu.ar.
authors: Hugo D
authors: HD
authors: Lujan
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000940:Antigenic Variation / Q000187:drug effects; D022041:Euchromatin / Q000378:metabolism; D016829:Giardia lamblia / Q000166:cytology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects
chemical_list: D022041:Euchromatin; D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009243:NAD; D006655:Histone Deacetylases; D008239:Lysine
keywords: Cellular differentiation; Gene regulation; HDAC; Histone deacetylases; Histone marks; Histone methylases; Sirtuin