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Reference: Manish Kushwaha, (2010). TbISWI and its role in transcriptional control in Trypanosoma brucei. DPhil. University of Oxford.Citable link to this page:


TbISWI and its role in transcriptional control in Trypanosoma brucei

Abstract: ISWI is a member of a versatile family of ATP-dependent chromatin remodelling complexes involved not only in transcription regulation (initiation, elongation and termination), but also in other cellular functions like maintenance of higher order chromatin structure and DNA replication. TbISWI, a novel ATPase of the ISWI family in Trypanosoma brucei, is involved in the transcriptional repression of silent VSG expression sites (ESs) in both bloodstream form (BF) and procyclic form (PF) life cycle stages of the parasite.Using in silico analysis, I have found that TbISWI is well conserved across the eukaryotic lineage, including those members of the order Kinetoplastida that do not exhibit antigenic variation. Compared to the ISWIs of higher eukaryotes, TbISWI has greater representation of random coils within its structure, an indicator of more structural fluidity and flexibility of interaction with multiple protein partners.Using an eGFP reporter based assay, I have studied the role of TbISWI in transcriptional repression of silent areas of the T. brucei genome. TbISWI was found to be involved in preventing inappropriate transcription of the silent VSG repertoires. TbISWI was also found to downregulate transcription in RNA pol I, but not pol II, transcription units. These results argue for the presence of at least two functionally distinct TbISWI complexes in T. brucei.Using DNA staining and fluorescence in situ hybridisation (FISH), I have investigated the potential effect of TbISWI depletion on cell cycle progression and minichromosome segregation. I did not find any evidence for the role of TbISWI in the maintenance of centromeric heterochromatin in T. brucei.

Digital Origin:Born digital Type of Award:DPhil Level of Award:Doctoral Awarding Institution: University of Oxford


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 Bibliographic Details

Issue Date: 2010

Copyright Date: 2010 Identifiers

Urn: uuid:36aedf26-7bbc-4f29-9fa5-fc57c9477c23 Item Description

Type: thesis;

Language: en Keywords: ISWI chromatin remodelling VSG expression sites African trypanosome trypanosomiasis transcriptional regulationSubjects: Biochemistry Parasitology Tiny URL: ora:6055


Autor: Dr Manish Kushwaha - institutionUniversity of Oxford facultyMedical Sciences Division - Biochemistry oxfordCollegeWolfson College

Fuente: https://ora.ox.ac.uk/objects/uuid:36aedf26-7bbc-4f29-9fa5-fc57c9477c23


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