TY  - JOUR
A1  - Batram, Christopher
A1  - Jones, Nivola G.
A1  - Janzen, Christian J.
A1  - Markert, Sebastian M.
A1  - Engstler, Markus
T1  - Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei
JF  - eLife
N2  - We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.
KW  - antigenic variation
KW  - expression site attenuation
KW  - developmental reprogramming
KW  - cell biology
KW  - genes and chromosomes
KW  - Trypanosoma brucei
KW  - variant surface glycoprotein (VSG)
KW  - monoallelic expression
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119727
SN  - 2050-084X
VL  - 3
IS  - e02324
ER  - 
TY  - JOUR
A1  - Pascoalino, Bruno
A1  - Dindar, Gülcin
A1  - Vieira-da-Rocha, João P.
A1  - Machado, Carlos Renato
A1  - Janzen, Christian J.
A1  - Schenkman, Sergio
T1  - Characterization of two different Asf1 histone chaperones with distinct cellular localizations and functions in Trypanosoma brucei
JF  - Nucleic Acids Research
N2  - 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.
KW  - chromatin assembly factors
KW  - DNA-damage checkpoint
KW  - tousled-like kinases
KW  - saccharomyes cerevisiae
KW  - gene expression
KW  - acetyltransferase RTT109
KW  - african trypanosomes
KW  - antigenetic variation
KW  - cycle regulation
KW  - nuclear import
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117220
SN  - 1362-4962
VL  - 42
IS  - 5
ER  -