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FRIBIO-Biologi og biomedisin

Gene regulation in the immune system: The TdT and pIgR genes as models to study the role of chromatin in transcriptional regulation.

Awarded: NOK 1.5 mill.

Transcriptional regulation of a mammalian gene depends on a complex interplay between the accessibility of the gene locus, the precise organization of regulatory DNA sequences, and the presence of regulatory factors, providing several steps of potential r egulation. Traditionally, studies of transcriptional regulation of mammalian genes have focused on identification of regulatory DNA elements using transient transfection and reporter gene assays. During the Ph.D. studies the project leader employed these assays, which are based on gene expression from a plasmid DNA template, to characterize the cytokine-mediated upregulation of the human pIgR gene. To advance our understanding of transcriptional regulation, it is important to analyze the regulation of ge nes when they are embedded in chromatin. The project leader therefore plan to spend part of the post-doctoral training in the laboratory of Dr. Stephen Smale who has established several methods to analyze changes in chromatin structure in relation to tran scriptional regulation. The project describes two cases studying transcriptional regulation of endogenous genes in the context of chromatin: Studies of LPS-induced expression of the IL-12 p40 gene (to be performed in Dr. Smale's laboratory), and expansio n of our ongoing studies of the cytokine-mediated regulation of the human pIgR gene (in collaboration with Dr. Johansen).

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FRIBIO-Biologi og biomedisin

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