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Title: Impact of STAT1 cooperative DNA binding on genomic binding site selection and subcellular dynamics
Author: Antunes, Filipa
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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Interferons (IFNs) are a family of cytokines that play an important role in the protection against pathogens and tumour cells. Transcription of most IFN target genes requires DNA binding of activated STATl dimers (pSTA Tl). In addition, cooperativity of pSTATl dimers on DNA, enabled by N-Domain (ND) interactions, has also been reported, but its biological significance has not been resolved. On the other hand, the study of protein dynamics in living cells has brought significant advances in systems biology, by disclosing molecular mechanisms that could only be perceived when the molecules are in their natural environment. Thus, this work presents a global analysis of STATl subcellular dynamics in living cells with major focus on the effects associated with STA T1 cooperative DNA binding, using a range of methodologies, including live-cell microscopy, kinetic modelling, biochemical experimentation and gene array technologies. Firstly, the implications of chromatin hyperacetylation and consequent relaxation on pSTATl nuclear mobility and vice-versa were studied, but no effects were found in either case. Moreover, STAT1 signalling regulation by a phosphorylation-acetylation switch mechanism was invalidated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available