title: NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei.
abstract: Trypanosoma brucei mono-allelically expresses one of approximately 1500 variant surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream. The active VSG is transcribed by RNA polymerase I in one of approximately 15 telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene expression predominantly post-transcriptionally, and how ESs are mono-allelically controlled remains a mystery. Here we identify a novel transcription regulator, which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45- to 65-fold derepression of the silent VSG221 ES. NLP is also involved in repression of transcription in the inactive VSG Basic Copy arrays, minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and 50-bp simple sequence repeats, the non-transcribed regions around rDNA and procyclin, and both active and silent ESs. Blocking NLP synthesis leads to downregulation of the active ES, indicating that NLP plays a role in regulating appropriate levels of transcription of ESs in both their active and silent state. Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control.
authors.affiliation: Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, UK.
authors.forename: Mani Shankar
authors.initials: MS
authors.lastname: Narayanan
authors.forename: Manish
authors.initials: M
authors.lastname: Kushwaha
authors.forename: Klaus
authors.initials: K
authors.lastname: Ersfeld
authors.forename: Alexander
authors.initials: A
authors.lastname: Fullbrook
authors.forename: Tara M
authors.initials: TM
authors.lastname: Stanne
authors.forename: Gloria
authors.initials: G
authors.lastname: Rudenko
mesh_terms: D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018503:Genome, Protozoan; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D056489:Nucleoplasmins / Q000737:chemistry; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000378:metabolism; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D056489:Nucleoplasmins; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma