Further Decryption of the Epigenetic Code

Scientists of the research unit Molecular Epigenetics, in collaboration with colleagues from other institutions, have decrypted mechanisms that control the cell nucleus enzyme RNA polymerase II so that selected genetic and epigenetic information is processed. The elucidation of such processes is a basis for better understanding diseases, and for developing new therapeutic approaches.

The central function of the enzyme RNA polymer­ase II is the transcription of genetic information stored in the DNA into mRNA, which then transports this information from the cell nucleus to the ribosomes and there regulates protein biosyn­thesis. In addition, however, RNA polymerase II – as has recently been discovered – is also crucial whenever epigenetic information is stored in the cell and retrieved again.

Scientists of the research unit Molecular Genetics, together with colleagues from Ludwig-Maximilians-Universität München and the Universities of Marseille and Barcelona, have explored important new details of these mechanisms. With many slight alterations of amino acids, cells are able to store information in the chromatin of the cell, in order to transcribe this later when needed or to delete it. The RNA polymerase II is directly involved in this process with its carboxy terminal domain (CTD) – a sequence of seven amino acids repeated 52 times.

As Dirk Eick and his colleagues have now found, not only are the serine amino acids reversibly modified in the CTD by means of phosphorylation, but also the amino acids threonine and tyrosine. The combinatorics of how the large number of these three amino acids is altered in the RNA polymerase II regulates important flows of information in the cell and is the central component for the regulation of gene expression in all multicellular organisms. The CTD of RNA polymerase II thus has the function of linking genetic and epigenetic information in the cell.

This further decryption of epigenetic mechanisms enables a better understanding of the molecular process of cell differentiation, as well as pathological and degenerative developments in the cells. Among other research questions, the scientists want to investigate how certain environmental factors can influence the cells epigenetically.

The term epigenetics refers to the genomic regulation mechanisms which are not specified in the DNA sequence. Epigenetic ­modifications, e.g. the methylation of histone components of the chromosomes, can contribute to determining the fate of genes and to a certain extent can be passed on to subsequent generations.

RNA Polymerase II (POL II) transcribes the information of all protein-coding genes into mRNA and is a central hub for storage and retrieval of epigenetic information in the cell. The carboxy terminal domain (CTD) thus links genetic and epigenetic information Source: HMGU