Schmitges, Frank W.. Histone methylation by PRC2 is inhibited by active chromatin marks. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10608
In this study we present an inhibitory mechanism that limits the spread of H3K27 methylation and protects active chromatin by breaking the positive feedback loop. PRC2 is allosterically inhibited by nucleosomes carrying active chromatin modifications such as H3K4me3 or H3K36me2/3. The mechanism is conserved in mammals, flies and even plants. In addition plants have distinct PRC2 subcomplexes and can modulate their specificity by the choice of the Su(z)12 homologue. Furthermore, we have identified Nurf55 as another histone binding module in the PRC2 complex that recognizes unmodified histone H3 but not H3K4me3.
Taken together, H3K27 methylation presents itself as a typical bistable switch. It is driven by the positive feedback loop in PRC2 activation and limited by active mark inhibition. Numerous chromatin modifying complexes recognize their own products and positive feedback loops are a common mechanism. We postulate that all these complexes need an additional inhibitory switch that prevents spreading of histone modifications over the entire genome.
|Committee Members:||Thomä, Nicolas and Fischle, Wolfgang|
|Faculties and Departments:||03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe > Urologie Kliniken BL (Gasser)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||117 p.|
|Last Modified:||30 Jun 2016 10:54|
|Deposited On:||09 Dec 2013 12:22|
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