Fungal DNA modifications and their role in gene regulation

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Fruiting bodies of the fungus Phycomyces blakesleeanus
Fruiting bodies of the fungus Phycomyces blakesleeanus
Nature makes public the study of a team with international participation coordinated by staff from the University of Seville.

A research team with international participation and coordinated by Professor Luis Corrochano, from the University of Seville, has made a significant advance in the understanding of gene regulation in fungi, discovering a DNA modification previously observed only in bacteria and some unicellular organisms. This finding has crucial implications for the development of new antifungals and the production of biofuels.

The team, which is also coordinated by Professor V. Garre of the University of Murcia, is made up of researchers from several North American laboratories, including the Joint Genome Institute of the U.S. Department of Energy. They have characterized the abundance of 6mA and 5mC in a wide variety of fungi, publishing their results in the prestigious journal Nature Communications.

The researchers found that 6mA clusters near the start of genes, facilitating access of proteins that activate these genes. In the fungus Phycomyces blakesleeanus, genes activated by light or during cell differentiation have a higher amount of 6mA, confirming its role in gene regulation. In contrast, 5mC represses gene activity and could serve as a mechanism to prevent the activity of transposons, DNA segments that can alter the structure and function of the genome if not properly controlled.

The fungus Mucor lusitanicus, a human pathogen and lipid producer, was crucial in these studies. Mutants in different methylase genes allowed the identification of the proteins responsible for adenine methylation. Some mutants showed alterations in their growth, underlining the importance of this modification. Analysis of the MetB protein suggests that the gene responsible for this function in fungi comes from a bacterium that parasitized an ancestor of Mucor.

This knowledge about DNA modifications and the proteins that regulate them opens new avenues for the development of antifungals and the improvement of lipid production, essential for the generation of biofuels. The study involved the participation of researchers María Corrochano Luque, Gabriel Gutiérrez Pozo, David Cánovas López and Luis M. Corrochano Peláez from the Department of Genetics of the University of Seville.