Author
Stefan Kubicek
Other affiliations: Medical University of Vienna, Howard Hughes Medical Institute, Research Institute of Molecular Pathology ...read more
Bio: Stefan Kubicek is an academic researcher from Austrian Academy of Sciences. The author has contributed to research in topics: Chromatin & Histone methyltransferase. The author has an hindex of 36, co-authored 105 publications receiving 8506 citations. Previous affiliations of Stefan Kubicek include Medical University of Vienna & Howard Hughes Medical Institute.
Topics: Chromatin, Histone methyltransferase, Epigenetics, Histone, Epigenomics
Papers published on a yearly basis
Papers
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TL;DR: An evolutionarily conserved pathway between histone H3-K9 methylation and DNA methylation in mammals is demonstrated and both methylation systems are likely to be important in reinforcing the stability of heterochromatic subdomains and thereby in protecting genome integrity.
1,247 citations
TL;DR: The data underscore the selective presence of distinct histone lysine methylation states in partitioning chromosomal subdomains but also reveal a surprising plasticity in propagating methylation patterns in eukaryotic chromatin.
1,129 citations
TL;DR: In this article, the authors identify a biologically active HMTase inhibitor that allows for the transient modulation of H3K9me2 marks in mammalian chromatin and demonstrate that transient incubation of several cell lines with BIX-01294 lowers bulk H3 K 9me2 levels that are restored upon removal of the inhibitor.
816 citations
TL;DR: A lysine methyltransferase, Smyd2, is reported that methylates a previously unidentified site, Lys 370, in p53, which is repressing to p53-mediated transcriptional regulation and providing regulatory cross-talk between post-translational modifications.
Abstract: Specific sites of lysine methylation on histones correlate with either activation or repression of transcription The tumour suppressor p53 (refs 4-7) is one of only a few non-histone proteins known to be regulated by lysine methylation Here we report a lysine methyltransferase, Smyd2, that methylates a previously unidentified site, Lys 370, in p53 This methylation site, in contrast to the known site Lys 372, is repressing to p53-mediated transcriptional regulation Smyd2 helps to maintain low concentrations of promoter-associated p53 We show that reducing Smyd2 concentrations by short interfering RNA enhances p53-mediated apoptosis We find that Set9-mediated methylation of Lys 372 inhibits Smyd2-mediated methylation of Lys 370, providing regulatory cross-talk between post-translational modifications In addition, we show that the inhibitory effect of Lys 372 methylation on Lys 370 methylation is caused, in part, by blocking the interaction between p53 and Smyd2 Thus, similar to histones, p53 is subject to both activating and repressing lysine methylation Our results also predict that Smyd2 may function as a putative oncogene by methylating p53 and repressing its tumour suppressive function
566 citations
TL;DR: It is shown that Xist recruits PRC1 components by both PRC2 dependent and independent modes and in the absence ofPRC2 function is sufficient for the establishment of Polycomb‐based memory systems in X inactivation.
Abstract: In mammals X inactivation is initiated by expression of Xist RNA and involves the recruitment of Polycomb repressive complex 1 (PRC1) and 2 (PRC2), which mediate chromosome-wide ubiquitination of histone H2A and methylation of histone H3, respectively. Here, we show that PRC1 recruitment by Xist RNA is independent of gene silencing. We find that Eed is required for the recruitment of the canonical PRC1 proteins Mph1 and Mph2 by Xist. However, functional Ring1b is recruited by Xist and mediates ubiquitination of histone H2A in Eed deficient embryonic stem (ES) cells, which lack histone H3 lysine 27 tri-methylation. Xist expression early in ES cell differentiation establishes a chromosomal memory, which allows efficient H2A ubiquitination in differentiated cells and is independent of silencing and PRC2. Our data show that Xist recruits PRC1 components by both PRC2 dependent and independent modes and in the absence of PRC2 function is sufficient for the establishment of Polycomb-based memory systems in X inactivation.
429 citations
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: The surface of nucleosomes is studded with a multiplicity of modifications that can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA.
10,046 citations
TL;DR: High-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology are generated.
6,488 citations
Massachusetts Institute of Technology1, Broad Institute2, University of California, Los Angeles3, University of British Columbia4, Baylor College of Medicine5, Howard Hughes Medical Institute6, University of Washington7, Ludwig Institute for Cancer Research8, University of California, San Francisco9, University of Connecticut10, University of Zagreb11, University of Texas at Austin12, Washington University in St. Louis13, University of Queensland14, Harvard University15, Cold Spring Harbor Laboratory16, University of Southern California17, University of California, Santa Cruz18, Simon Fraser University19, Morgridge Institute for Research20, University of Texas at Dallas21, National Institutes of Health22
TL;DR: It is shown that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
5,037 citations