The Department of Biomedicine

BBB seminar: Reidunn B. Aalen

Epigenetic gene regulation: The 'conspiracy' between chromatin modification and transcription factors

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Reidunn B. Aalen
Department of Molecular Biosciences, University of Oslo

An important aspect of gene regulation involves the interconversion between transcriptionally permissive euchromatin and repressive heterochromatin, which in part is regulated by post-translational modifications of the nucleosomal histone tails. The patterns of histone modification (the histone code) are thought to create binding sites for proteins that facilitate or restrict transcription. While histone acetylation is generally associated with permissive chromatin, histone methylation patterns correlate with active, permissive, or repressed chromatin. DNA methylation of cytosines, the second type of epigenetic marks, is associated with repression of transcription and may be functionally interlinked with histone methylation. As patterns of histone modification and DNA methylation can be stable through many cell generations, they can serve as a mechanism for cellular memory. Methylation of conserved lysines on the histone tails is mediated by SET-domain histone methyltransferases (HMTases). The properties of HMTases depend on their histone tail specificities. Eleven classes of SET-domain proteins have been identified, some of which play a crucial role in control of heterochromatinization and maintenance of correct gene expression patterns. It is less clear how HMTases are targeted to genes in chromatin. One possibility is that certain transcription factors recruit particular HMTases.

In this FUGE project we will use Arabidopsis thaliana as a model for investigating the interdependency between HMTases and transcription factors. We will use mutants of selected SET-domain genes and transcription factor genes in transcriptional profiling of the complete gene set of Arabidopsis and ChIP-on-chip assays using genomic tiling arrays to identify how HMTases and transcription factors 'conspire' to regulate target genes. Proteins interacting with HMTases will be identified to explore further molecular events at the targets.

We expect that our project will reveal not only new insight on the function of Arabidopsis HMTases, but also on related enzymes in other organisms. Given that the basic molecular mechanisms underlying epigenetic gene regulation are conserved from yeasts to plants and animals, we expect that results from this project will have relevance for our understanding of the epigenetic contribution to gene regulation in general. The project is designed to identify elements of regulatory circuits which will subsequently be used to develop a model for a regulatory network and thus form the basis for systems biological research.

Data on selected Arabidopsis SET-domain proteins generated using bioinformatics, genetics and biochemistry will be presented.

Host: Marit Bakke <marit.bakke[@]biomed.uib.no>, Department of Biomedicine