13. Nov 2025
Epigenetics in development, aging, health and disease, and the future of medical research
Datum: 13. November 2025 |
15:00 –
16:00
Sprecher:
Susan M. GASSER
Veranstaltungsort: Central Bldg / Ground Floor / Ballroom
Sprache:
Englisch
Segregation of genomic regions into accessible euchromatin and inaccessible heterochromatin is essential for temporal and tissue-specific gene transcription. This is true across all eukaryotic organisms and it is particularly pronounced in vertebrates and mammals, where satellite repeat DNA, transposable elements (remnants of invasive retroviral and DNA viral elements), and simple repeats occupy up to 70% of the genome. We have examined the loss of the major repressive epigenetic mark in C. elegans, that is di- and tri-methylation of lysine 9 of histone H3 , which is a conserved nucleosomal marker for compacted and transcriptionally repressed heterochromatin. We show that loss of the SETDB1 homolog (MET-2) derepresses satellite repeats, transposable elements and tissue-specific genes by demethylating histone H3 K9. Animals lacking met-2 show a loss of fertility, have delays in development, and shortened lifespan, and show the promiscuous transcription of repeat DNA and formation of RNA-DNA hybrids on what are normally non transcribed repeats. This HMT is highly regulated and forms nuclear foci through physical interaction with an intrinsically disordered protein LIN-65. Loss of the second H3K9 HMT in worms, SET-25, leads to the expression of full length retroviral elements and has the unique role of initiating de novo repression of invading retroviruses.
The pattern of gene deregulation by loss of heterochromatin depends on the tissue studied, and the patterns of genes misexpressed is distinct in embryos, muscle, skin and gut, although in all differentiated tissues tested, the genes that determine the germline are aberrantly derepressed. However aberrant gene expression upon the loss of heterochromatin structure requires the presence of activating transcription factors (TFs), and especially for the activation of silent tissue-specific genes, the recruitment of a strong histone acetyltransferase – p300/CBP. It will be discussed how the loss of the integrity of both repressive and activating epigenetic factors triggers both disease and aging. In the final few minutes of the talk a view of the future of medical research and health care in Europe will be discussed.
