Max Planck Institute of Immunobiology and Epigenetics
Laboratory Thomas Jenuwein
Epigenetic control by histone lysine methylation
In the nuclei of almost all eukaryotic cells genomic DNA is compacted with histone and non-histone proteins in a dynamic polymer called chromatin. Several epigenetic mechanisms, such as nucleosome remodeling, histone modifications, DNA methylation and non-coding RNA function together to organize chromatin into accessible (euchromatic) and inaccessible (heterochromatic) domains. We discovered the Suv39h enzymes as the first histone lysine methyltransferases (KMT) and have shown that Suv39h-dependent histone H3 lysine 9 (H3K9me3) methylation is a central epigenetic modification for a repressed chromatin state at heterochromatic regions.
The goal of our research is to dissect epigenetic gene regulation and to identify the underlying mechanisms that initiate and maintain heterochromatin in mammalian cells (Figure 1).
Since heterochromatin has important functions in safe-guarding genome integrity, in silencing of endogenous retroviruses and in stabilizing gene expression programs, our research is of crucial importance for a better understanding of normal and perturbed development and for new insights to protect from disease progression.
Duda K, Ching R, Jerabek L, Shukeir N, Erikson G, Engist B, Onishi-Seebacher M, Perrera V, Richter F, Mittler G, Fritz K, Helm M, Knuckles P, Bühler M, Jenuwein T (2021)
m6A RNA methylation of major satellite repeat transcripts facilitates chromatin association and RNA:DNA hybrid formation in mouse heterochromatin.
Bulut-Karslioglu A, De La Rosa-Velázquez IA, Ramirez F, Barenboim M, Onishi-Seebacher M, Arand J, Galán C, Winter GE, Engist B, Gerle B, O'Sullivan RJ, Martens JH, Walter J, Manke T, Lachner M, Jenuwein T (2014)
Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells.