HMGN proteins promote chromatin unfolding, enhance access to nucleosomes, and modulate transcription from chromatin templates. A major question is whether HMGN proteins act indiscriminately as general facilitators of transcription, or whether they act specifically to regulate the expression of particular target genes. Furthermore, the lack of known gene targets has hampered research into how HMGN proteins modulate transcription in vivo.
This proposal focuses on a new member of the HMGN family, HMGN3a, and its splice variant, HMGN3b. In my postdoctoral studies at the NIH in the U.S.A., I identified several gene targets for HMGN3. I have recently taken up a lectureship at the University of Glasgow in the UK, with the aim of establishing my own research laboratory. My start-up funding is very limited, and I am applying for an IRG to help fund my research and thus promote my integration into the European Research community. I propose to build upon my previous research and use one of the HMGN3 target genes, the chemokine IP-10, as a model system to investigate the mechanism of action of HMGN3. I have created cell lines in which the expression of HMGN3a or b can be induced by doxycycline. This is a highly controlled system for studying the role of HMGN3a/b in vivo.
I will use these cell lines to further investigate the role HMGN3a/b in cytokine-induced gene expression. I will then use chromatin immunoprecipitation (ChIP) assays to investigate where HMGN3 binds to the IP-10 gene in vivo, and whether this correlates with the profile of histone modifications across the locus. I will assay DNA accessibility over the gene to determine whether HMGN3 plays a role in unfolding chromatin. I will also investigate whether HMGN3 alters the rate or extent of transcription factor binding using in vivo foot-printing and ChIP assays. Finally, I will investigate whether HMGN3 is phosphorylated in response to cytokine signalling.
Field of science
- /medical and health sciences/health sciences/public and environmental health/epidemics prevention/immunisation
- /natural sciences/biological sciences/genetics and heredity/dna
- /natural sciences/biological sciences/biochemistry/biomolecules/proteins
- /natural sciences/biological sciences/genetics and heredity/chromosome
- /medical and health sciences/basic medicine/immunology
- /medical and health sciences/clinical medicine/cancer
Call for proposal
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