Obiettivo
Chromatin insulators allow genes to maintain independent programmes of expression through the establishment of fixed chromatin boundaries. Vertebrate insulators have been found to regulate the expression of genes with functions from growth control and development to X-inactivation. The properties of insulators have been extensively characterised, but their mechanism of action is largely undetermined. The HS4 element from the chicken b-globin locus is the paradigm vertebrate insulator. Flanking transgenes with HS4 has proved useful in the generation of many transgenic animal and cell lines, by allowing uniform transgene expression in all tissue types.
The aim of this proposal is to determine the mechanism(s) of insulator action. In my postdoctoral studies at the NIH (USA), I identified the first known insulator-binding proteins from vertebrates. I have recently taken up a lectureship at the University of Glasgow where I am establishing an independent research group to study chromatin insulator elements and gene regulation. I have minimal start-up funding, so I am applying for an IRG to help establish my research programme, thus promoting my re-integration into the European Research Area.
The proposed work will focus on a new protein, called BGP1 that interacts with several binding sites within the HS4 element. BGP1 binding sites are required for the barrier activity of HS4. BGP1 binding sites are also required for the prevention of CpG DNA methylation, an epigenetic determinant of stable gene silencing. This is of broad interest as the promoters of tumour suppressor genes become aberrantly methylated and transcriptionally silenced in cancer. It is conceivable that BGP1 recruits a factor that mediates immunity from DNA methylation. I will purify BGP1-interacting proteins in order to identify factors that mediate BGP1-directed functions. I will also use BGP1 as bait to identify novel insulator elements to compare with the HS4 element.
Campo scientifico
Parole chiave
Invito a presentare proposte
FP6-2002-MOBILITY-12
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