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FUGE-Funksjonell genomforskn.i Norg

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

Tildelt: kr 5,3 mill.

Prosjektnummer:

183609

Søknadstype:

Prosjektperiode:

2007 - 2013

Geografi:

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 patte rns 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 modific ation and DNA methylation can be stable through many cell generations, they can serve as a mechanism for cellular memory. Methylation of conserved lysins on the histone tails is mediated by SET domain histone methyltransferases (HMTases). The properties o f 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 h ow HMTases are targeted to genes in chromatin. One possibility is that certain transcription factors recruit particular HMTases. In this project we will use Arabidopsis thaliana as model for investigating the interdependency between HMTases, transcription factors and DNA methylation. 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.

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FUGE-Funksjonell genomforskn.i Norg