Research summary
The goal of our laboratory is to understand how eukaryotic cells establish,
maintain and inherit functionally distinct domains of gene expression
within their genomes. The genes in certain genomic regions can become
permanently repressed or silenced, a mechanism that is used to ensure
appropriate gene expression, for instance during development.
Learning about the mechanisms of epigenetic gene silencing is of fundamental
importance for understanding the aging of cells and the abnormalities
in this process that can cause malignant transformation.
The formation of silenced chromatin requires the concerted packaging
of DNA into chromatin with specifically modified histones as well
as with non-histone proteins at a given time during the cell cycle
(see Fig.). After DNA replication, chromatin assembly complexes (e.g.
CAF-I) restore chromatin on freshly replicated DNA. One question is
how modification patterns on "old" chromatin (e.g. histone
acetylation patterns) are reestablished on newly formed chromatin.
We are using
the small eukaryote Saccharomyces cerevisiae to study the molecular
determinants of silencing and to investigate the relationship between
DNA replication and the formation of repressed chromatin.
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Fig.: DNA
in the eukaryotic nucleus is packaged with histones and other
proteins into chromatin. After replication, newly synthesized
histones (yellow) carrying acetylation patterns different
from old histones (orange) are incorporated into chromatin
by chromatin assembly complexes. The aminoterminal acetylation
pattern of histones (red balls) influences the binding of
non-histone proteins to chromatin. Generally, deacetylated
histones are correlated with compact chromatin, and thus,
with lower gene expression.
 Gene silencing in yeast
Histone acetylation, HATs and HDACs
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Otto-Warburg Laboratory