A novel ISWI is involved in VSG expression site downregulation in African trypanosomes

African trypanosomes show monoallelic expression of one of about 20 telomeric variant surface glycoprotein (VSG) gene‐expression sites (ESs) while multiplying in the mammalian bloodstream. We screened for genes involved in ES silencing using flow cytometry and RNA interference (RNAi). We show that a...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2007-05, Vol.26 (9), p.2400-2410
Main Authors: Hughes, Katie, Wand, Matthew, Foulston, Lucy, Young, Rosanna, Harley, Kate, Terry, Stephen, Ersfeld, Klaus, Rudenko, Gloria
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - physiology
Alleles
Amino Acid Sequence
Animals
antigenic variation
Cell Nucleus - metabolism
Down-Regulation
Gene expression
Gene Silencing
Glycoproteins
ISWI
Molecular biology
Molecular Sequence Data
monoallelic expression
Promoter Regions, Genetic
Protein Structure, Tertiary
Proteins
regulated domains
Ribonucleic acid
RNA
RNA Interference
Transcription Factors - physiology
Trypanosoma brucei
Trypanosoma brucei brucei - genetics
Trypanosoma brucei brucei - physiology
Variant Surface Glycoproteins, Trypanosoma - biosynthesis
Variant Surface Glycoproteins, Trypanosoma - genetics
Variant Surface Glycoproteins, Trypanosoma - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:African trypanosomes show monoallelic expression of one of about 20 telomeric variant surface glycoprotein (VSG) gene‐expression sites (ESs) while multiplying in the mammalian bloodstream. We screened for genes involved in ES silencing using flow cytometry and RNA interference (RNAi). We show that a novel member of the ISWI family of SWI2/SNF2‐related chromatin‐remodelling proteins (TbISWI) is involved in ES downregulation in Trypanosoma brucei. TbISWI has an atypical protein architecture for an ISWI, as it lacks characteristic SANT domains. Depletion of TbISWI by RNAi leads to 30–60‐fold derepression of ESs in bloodstream‐form T. brucei, and 10–17‐fold derepression in insect form T. brucei. We show that although blocking synthesis of TbISWI leads to derepression of silent VSG ES promoters, this does not lead to fully processive transcription of silent ESs, or an increase in ES‐activation rates. VSG ES activation in African trypanosomes therefore appears to be a multistep process, whereby an increase in transcription from a silent ES promoter is necessary but not sufficient for full ES activation.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601678