Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H||WB, PIA, DB, Mplex||Rb||Culture Supernatant||Monoclonal Antibody|
|Presentation||Cultured supernantant containing 0.05% sodium azide|
|Safety Information according to GHS|
|Material Size||100 µL|
|Reference overview||Pub Med ID|
|Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation.|
Rothbart, SB; Krajewski, K; Nady, N; Tempel, W; Xue, S; Badeaux, AI; Barsyte-Lovejoy, D; Martinez, JY; Bedford, MT; Fuchs, SM; Arrowsmith, CH; Strahl, BD
Nature structural & molecular biology 19 1155-60 2012
A fundamental challenge in mammalian biology has been the elucidation of mechanisms linking DNA methylation and histone post-translational modifications. Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has multiple domains that bind chromatin, and it is implicated genetically in the maintenance of DNA methylation. However, molecular mechanisms underlying DNA methylation regulation by UHRF1 are poorly defined. Here we show that UHRF1 association with methylated histone H3 Lys9 (H3K9) is required for DNA methylation maintenance. We further show that UHRF1 association with H3K9 methylation is insensitive to adjacent H3 S10 phosphorylation--a known mitotic 'phospho-methyl switch'. Notably, we demonstrate that UHRF1 mitotic chromatin association is necessary for DNA methylation maintenance through regulation of the stability of DNA methyltransferase-1. Collectively, our results define a previously unknown link between H3K9 methylation and the faithful epigenetic inheritance of DNA methylation, establishing a notable mitotic role for UHRF1 in this process.
|A novel role for the Aurora B kinase in epigenetic marking of silent chromatin in differentiated postmitotic cells.|
Sabbattini, P; Canzonetta, C; Sjoberg, M; Nikic, S; Georgiou, A; Kemball-Cook, G; Auner, HW; Dillon, N
The EMBO journal 26 4657-69 2007
Combinatorial modifications of the core histones have the potential to fine-tune the epigenetic regulation of chromatin states. The Aurora B kinase is responsible for generating the double histone H3 modification tri-methylated K9/phosphorylated S10 (H3K9me3/S10ph), which has been implicated in chromosome condensation during mitosis. In this study, we have identified a novel role for Aurora B in epigenetic marking of silent chromatin during cell differentiation. We find that phosphorylation of H3 S10 by Aurora B generates high levels of the double H3K9me3/S10ph modification in differentiated postmitotic cells and also results in delocalisation of HP1beta away from heterochromatin in terminally differentiated plasma cells. Microarray analysis of the H3K9me3/S10ph modification shows a striking increase in the modification across repressed genes during differentiation of mesenchymal stem cells. Our results provide evidence that the Aurora B kinase has a role in marking silent chromatin independently of the cell cycle and suggest that targeting of Aurora B-mediated phosphorylation of H3 S10 to repressed genes could be a mechanism for epigenetic silencing of gene expression.
|Binary switches and modification cassettes in histone biology and beyond.|
Fischle, Wolfgang, et al.
Nature, 425: 475-9 (2003) 2003
An immense number of post-translational modifications on histone proteins have been described and additional sites of modification are still being uncovered. Whereas many direct and indirect connections between certain histone modifications and distinct biological phenomena have now been established, concepts for comprehending the extreme density and variety of these covalent modifications are lacking. Here, we formally introduce localized 'binary switches' and 'modification cassettes' as new concepts in histone biology, elucidating mechanisms that might govern the biological readout of distinct modification patterns. Specifically, our hypotheses provide missing models for the dynamic readout of stable histone modifications and offer explanations for several long-standing questions embedded in the literature. Our ideas might also apply to non-histone proteins and are open to direct experimental examination.