title: Characterization of two different Asf1 histone chaperones with distinct cellular localizations and functions in Trypanosoma brucei.
abstract: The anti-silencing function protein 1 (Asf1) is a chaperone that forms a complex with histones H3 and H4 facilitating dimer deposition and removal from chromatin. Most eukaryotes possess two different Asf1 chaperones but their specific functions are still unknown. Trypanosomes, a group of early-diverged eukaryotes, also have two, but more divergent Asf1 paralogs than Asf1 of higher eukaryotes. To unravel possible different functions, we characterized the two Asf1 proteins in Trypanosoma brucei. Asf1A is mainly localized in the cytosol but translocates to the nucleus in S phase. In contrast, Asf1B is predominantly localized in the nucleus, as described for other organisms. Cytosolic Asf1 knockdown results in accumulation of cells in early S phase of the cell cycle, whereas nuclear Asf1 knockdown arrests cells in S/G2 phase. Overexpression of cytosolic Asf1 increases the levels of histone H3 and H4 acetylation. In contrast to cytosolic Asf1, overexpression of nuclear Asf1 causes less pronounced growth defects in parasites exposed to genotoxic agents, prompting a function in chromatin remodeling in response to DNA damage. Only the cytosolic Asf1 interacts with recombinant H3/H4 dimers in vitro. These findings denote the early appearance in evolution of distinguishable functions for the two Asf1 chaperons in trypanosomes.
authors: Depto. de Microbiologia, Imunologia e Parasitologia, UNIFESP, Rua Pedro de Toledo 669 L6A, São Paulo, São Paulo 04039-032, Brazil, Lehrstuhl für Zell- und Entwicklungsbiologie, Theodor-Boveri-Institut, Biozentrum der Universität Würzburg, Am Hubland, 97074 Würzburg, Germany and Depto. de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, CP 4861, 30161-970, Belo Horizonte, Minas Gerais, Brazil.
authors: Bruno
authors: B
authors: Pascoalino
authors: Gülcin
authors: G
authors: Dindar
authors: João P
authors: JP
authors: Vieira-da-Rocha
authors: Carlos Renato
authors: CR
authors: Machado
authors: Christian J
authors: CJ
authors: Janzen
authors: Sergio
authors: S
authors: Schenkman
mesh_terms: D000107:Acetylation; D002453:Cell Cycle; D004249:DNA Damage; D056488:Histone Chaperones / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D006657:Histones / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D015800:Protozoan Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000378:metabolism*
chemical_list: D056488:Histone Chaperones; D006657:Histones; D020033:Protein Isoforms; D015800:Protozoan Proteins