TDP1 is an HMG chromatin protein facilitating RNA polymerase I transcription in African trypanosomes.
Unusually for a eukaryote, Trypanosoma brucei transcribes its variant surface glycoprotein (VSG) gene expression sites (ESs) in a monoallelic fashion using RNA polymerase I (Pol I). It is still unclear how ES transcription is controlled in T. brucei. Here, we show that the TDP1 architectural chromatin protein is an essential high mobility group box (HMGB) protein facilitating Pol I transcription in T. brucei. TDP1 is specifically enriched at the active compared with silent VSG ES and immediately downstream of ribosomal DNA promoters and is abundant in the nucleolus and the expression site body subnuclear compartments. Distribution of TDP1 at Pol I-transcribed loci is inversely correlated with histones. Depletion of TDP1 results in up to 40-90% reduction in VSG and rRNA transcripts and a concomitant increase in histones H3, H2A and H1 at these Pol I transcription units. TDP1 shares features with the Saccharomyces cerevisiae HMGB protein Hmo1, but it is the first architectural chromatin protein facilitating Pol I-mediated transcription of both protein coding genes as well as rRNA. These results show that TDP1 has a mutually exclusive relationship with histones on actively transcribed Pol I transcription units, providing insight into how Pol I transcription is controlled.
Division of Cell and Molecular Biology, Imperial College London, South Kensington, London SW7 2AZ, UK.
Mani Shankar
MS
Narayanan
Gloria
G
Rudenko
D002466:Cell Nucleolus / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012318:RNA Polymerase I / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016053:RNA, Protozoan / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; D006657:Histones; D015800:Protozoan Proteins; D012333:RNA, Messenger; D016053:RNA, Protozoan; D014643:Variant Surface Glycoproteins, Trypanosoma; D012318:RNA Polymerase I; D010727:Phosphoric Diester Hydrolases