Cohesin regulates VSG monoallelic expression in trypanosomes.
Antigenic variation allows Trypanosoma brucei to evade the host immune response by switching the expression of 1 out of approximately 15 telomeric variant surface glycoprotein (VSG) expression sites (ESs). VSG ES transcription is mediated by RNA polymerase I in a discrete nuclear site named the ES body (ESB). However, nothing is known about how the monoallelic VSG ES transcriptional state is maintained over generations. In this study, we show that during S and G2 phases and early mitosis, the active VSG ES locus remains associated with the single ESB and exhibits a delay in the separation of sister chromatids relative to control loci. This delay is dependent on the cohesin complex, as partial knockdown of cohesin subunits resulted in premature separation of sister chromatids of the active VSG ES. Cohesin depletion also prompted transcriptional switching from the active to previously inactive VSG ESs. Thus, in addition to maintaining sister chromatid cohesion during mitosis, the cohesin complex plays an essential role in the correct epigenetic inheritance of the active transcriptional VSG ES state.
Landeira
David
D
Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Cientificas, 18100 Granada, Spain.
Bart
Jean-Mathieu
JM
Van Tyne
Daria
D
Navarro
Miguel
M
D000818:Animals; D000940:Antigenic Variation; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D005786:Gene Expression Regulation; D046911:Macromolecular Substances / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D014158:Transcription, Genetic; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000276:immunology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics* / Q000276:immunology; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D046911:Macromolecular Substances; D021122:Protein Subunits; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; D000097722:Cohesins