Floor Frederiks

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Bites by Loxosceles spiders can produce severe clinical symptoms, including dermonecrosis, thrombosis, vascular leakage, hemolysis, and persistent inflammation. The causative factor is a sphingomyelinase D (SMaseD) that cleaves sphingomyelin into choline and ceramide 1-phosphate. A similar enzyme, showing comparable bioactivity, is secreted by certain(More)
Dot1 methylates histone H3 lysine 79 (H3K79) on the nucleosome core and is involved in Sir protein-mediated silencing. Previous studies suggested that H3K79 methylation within euchromatin prevents nonspecific binding of the Sir proteins, which in turn facilitates binding of the Sir proteins in unmethylated silent chromatin. However, the mechanism by which(More)
Whereas mono-, di- and trimethylation states of lysines on histones typically have specific functions, no specific functions have been attributed so far to the different methylation states of histone H3 Lysine 79 (H3K79) generated by Dot1. Here we show that Dot1, in contrast to other known histone methyltransferases, introduces multiple methyl groups via a(More)
Post-translational modifications of histone proteins have a crucial role in regulating gene expression. If efficiently re-established after chromosome duplication, histone modifications could help propagate gene expression patterns in dividing cells by epigenetic mechanisms. We used an integrated approach to investigate the dynamics of the conserved(More)
Methylation of histone H3 lysine 79 (H3K79) by Dot1 is highly conserved among species and has been associated with both gene repression and activation. To eliminate indirect effects and examine the direct consequences of Dot1 binding and H3K79 methylation, we investigated the effects of targeting Dot1 to different positions in the yeast genome. Targeting(More)
Dot1 is a highly conserved methyltransferase that modifies histone H3 on the nucleosome core surface. In contrast to yeast, flies, and humans where a single Dot1 enzyme is responsible for all methylation of H3 lysine 79 (H3K79), African trypanosomes express two DOT1 proteins that methylate histone H3K76 (corresponding to H3K79 in other organisms) in a(More)
In the eukaryotic cell nucleus, the DNA is packaged in a structure called chromatin. The fundamental building block of chromatin is the nucleosome, which is composed of DNA wrapped around an octamer of four distinct histone proteins. Post-translational modifications (PTMs) of histone proteins can affect chromatin structure and function and thereby play(More)
Dot1 is a conserved histone methyltransferase that methylates histone H3 on lysine 79. We previously observed that in Saccharomyces cerevisiae, a single DOT1 gene encodes two Dot1 protein species. Here, we show that the relative abundance of the two isoforms changed under nutrient-limiting conditions. A mutagenesis approach showed that the two Dot1 isoforms(More)
Thank you for the submission of your research manuscript to EMBO reports. It has been sent to three referees, and so far we have received reports from two of them, which I copy below. As both referees feel that the manuscript is interesting and recommend that you should be given a chance to revise it, I would like to ask you to begin revising your(More)
News about old histones: A role for histone age in controlling the epigenome Fred van Leeuwen, Floor Frederiks, Marit Terweij, Dirk De Vos & Barbara M. Bakker a Division of Gene Regulation; Netherlands Cancer Institute; Amsterdam, The Netherlands b Biology Department; University of Antwerp; Antwerp, Belgium c Department of Pediatrics; Center for Liver,(More)
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