PMID- 10205179 OWN - NLM STAT- MEDLINE DCOM- 19990611 LR - 20220316 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 18 IP - 8 DP - 1999 Apr 15 TI - Trypanosoma brucei variant surface glycoprotein regulation involves coupled activation/inactivation and chromatin remodeling of expression sites. PG - 2265-72 AB - Trypanosoma brucei is an extracellular protozoan parasite that cycles between mammalian hosts and the tsetse vector. In bloodstream-form trypanosomes, only one variant surface glycoprotein gene (VSG) expression site (ES) is active at any time. Transcriptional switching between ESs results in antigenic variation. No VSG is transcribed in the insect procyclic stage. We have used bacteriophage T7 RNA polymerase (T7RNAP) to study the transcriptional accessibility of ES chromatin in vivo. We show that T7RNAP-mediated transcription from chromosomally integrated T7 promoters is repressed along the entire length of the ES in the procyclic form, but not in the bloodstream form, suggesting that the accessible chromatin of inactive bloodstream-form ESs is remodeled upon differentiation to yield a structure that is no longer permissive for T7RNAP-mediated transcription. In the bloodstream form, replacing the active ES promoter with a T7 promoter, which is incapable of sustaining high-level transcription of the entire ES, prompts an ES switch. These data suggest two distinct mechanisms for ES regulation: a chromatin-mediated developmental silencing of the ES in the procyclic form and a rapid coupled mechanism for ES activation and inactivation in the bloodstream form. FAU - Navarro, M AU - Navarro M AD - Laboratory of Molecular Parasitology, The Rockefeller University (Box 185), 1230 York Avenue, New York, NY 10021-6399, USA. FAU - Cross, G A AU - Cross GA FAU - Wirtz, E AU - Wirtz E LA - eng GR - AI 21729/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Chromatin) RN - 0 (DNA Primers) RN - 0 (Variant Surface Glycoproteins, Trypanosoma) RN - 0 (Viral Proteins) RN - EC 2.7.7.- (bacteriophage T7 RNA polymerase) RN - EC 2.7.7.6 (DNA-Directed RNA Polymerases) SB - IM MH - Animals MH - Base Sequence MH - Chromatin/*metabolism MH - DNA Primers MH - DNA-Directed RNA Polymerases/genetics/metabolism MH - *Gene Expression Regulation MH - Promoter Regions, Genetic MH - *Transcription, Genetic MH - Trypanosoma brucei brucei/*metabolism MH - Variant Surface Glycoproteins, Trypanosoma/*genetics MH - Viral Proteins PMC - PMC1171309 EDAT- 1999/04/16 00:00 MHDA- 1999/04/16 00:01 PMCR- 2000/04/15 CRDT- 1999/04/16 00:00 PHST- 1999/04/16 00:00 [pubmed] PHST- 1999/04/16 00:01 [medline] PHST- 1999/04/16 00:00 [entrez] PHST- 2000/04/15 00:00 [pmc-release] AID - 10.1093/emboj/18.8.2265 [doi] PST - ppublish SO - EMBO J. 1999 Apr 15;18(8):2265-72. doi: 10.1093/emboj/18.8.2265.