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Promoter occupancy of the basal class I transcription factor A differs strongly between active and silent VSG expression sites in Trypanosoma brucei

Please always quote using this URN: urn:nbn:de:bvb:20-opus-117232
  • 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. TheMonoallelic 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.show moreshow less

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Metadaten
Author: Tu N. Nguyen, Laura S. M. Müller, Sung Hee Park, T. Nicolai Siegel, Arthur Günzl
URN:urn:nbn:de:bvb:20-opus-117232
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Parent Title (English):Nucleic Acid Research
ISSN:1362-4962
Year of Completion:2014
Volume:42
Issue:5
Pagenumber:3164-3176
Source:Nucleic Acids Research, 2014, Vol. 42, No. 5, 3164-3176. doi:10.1093/nar/gkt1301
DOI:https://doi.org/10.1093/nar/gkt1301
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24353315
Sonstige beteiligte Institutionen:Research Center of Infectious Diseases (ZINF) of the University of Wurzburg, Germany
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:RNA-polymerase-I; acrican trypanosomes; antigenic variation; blood-stream forms; complex; gene expression; plasmodium falciparum; ribosomal RNA; subunit; virulence genes
Release Date:2015/08/17
Licence (German):License LogoCC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell