TY  - JOUR
A1  - Nguyen, Tu N.
A1  - Müller, Laura S. M.
A1  - Park, Sung Hee
A1  - Siegel, T. Nicolai
A1  - Günzl, Arthur
T1  - Promoter occupancy of the basal class I transcription factor A differs strongly between active and silent VSG expression sites in Trypanosoma brucei
JF  - Nucleic Acid Research
N2  - Monoallelic expression within a gene family is found in pathogens exhibiting antigenic variation and in mammalian olfactory neurons. Trypanosoma brucei, a lethal parasite living in the human bloodstream, expresses variant surface glycoprotein (VSG) from 1 of 15 bloodstream expression sites (BESs) by virtue of a multifunctional RNA polymerase I. The active BES is transcribed in an extranucleolar compartment termed the expression site body (ESB), whereas silent BESs, located elsewhere within the nucleus, are repressed epigenetically. The regulatory mechanisms, however, are poorly understood. Here we show that two essential subunits of the basal class I transcription factor A (CITFA) predominantly occupied the promoter of the active BES relative to that of a silent BES, a phenotype that was maintained after switching BESs in situ. In these experiments, high promoter occupancy of CITFA was coupled to high levels of both promoter-proximal RNA abundance and RNA polymerase I occupancy. Accordingly, fluorescently tagged CITFA-7 was concentrated in the nucleolus and the ESB. Because a ChIP-seq analysis found that along the entire BES, CITFA-7 is specifically enriched only at the promoter, our data strongly indicate that monoallelic BES transcription is activated by a mechanism that functions at the level of transcription initiation.
KW  - RNA-polymerase-I
KW  - blood-stream forms
KW  - acrican trypanosomes
KW  - gene expression
KW  - antigenic variation
KW  - ribosomal RNA
KW  - plasmodium falciparum
KW  - virulence genes
KW  - subunit
KW  - complex
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117232
SN  - 1362-4962
VL  - 42
IS  - 5
ER  - 
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  -