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Unraveling the molecular mechanisms underlying genomic in trans interactions


The regulation of gene activity via the binding of protein factors to cis acting sequence elements is being studied in great detail. In contrast, little is known about gene regulation in trans, i.e. how sequences on one chromosome control the activity of a gene on another chromosome. There is mounting evidence that such trans regulatory systems are important in higher eukaryotes, including flies, plants and mammals. The aim of this research project is to unravel the molecular mechanism underlying trans gene regulation.

The regulatory system that will be used in this project is the naturally occurring trans inactivation system called paramutation. With paramutation, the trans interaction between high and low expressing epigenetic states of an allele leads to a heritable transcriptional down-regulation of the high expressing epigenetic state. Paramutation has been thoroughly studied in maize, mainly using classical genetics. Importantly, paramutation-like in trans gene regulation phenomena have been observed in other eukaryotes, including humans. The mechanism of paramutation is therefore most likely conserved in evolution, underscoring its importance.

In this project, the genetically well-characterized paramutation of maize b1 alleles is used. The maize system is currently being transferred to Arabidopsis, as the molecular tools available for maize are still limited, while they are ample for Arabidopsis. The transfer to Arabidopsis creates a unique opportunity for the systematic identification and characterization of: (i) the regulatory elements and (ii) the proteins and chromatin structure changes involved.

Results will give insight into the interplay of components and epigenetic changes and thereby the molecular mechanism involved in trans genomic interactions. The basic epigenetic control mechanisms are essentially the same in all higher eukaryotes. Therefore, the knowledge obtained in this project can be extended to other systems.

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