Histone Lysine Demethylases and Their Impact on Epigenetics

Howard Hughes Medical Institute, Department of Biochemistry, Division of Nucleic Acids Enzymology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Cell (Impact Factor: 32.24). 05/2006; 125(2):213-7. DOI: 10.1016/j.cell.2006.04.003
Source: PubMed


Chromatin establishes, maintains, and propagates different patterns of gene expression by storing and organizing genetic information. Histone lysine methylation has been regarded as a stable chromatin modification that together with DNA methylation defines epigenetic programs. Epigenetic phenomena are responsible for the non-Mendelian inheritance of phenotypic alterations. The recent discovery of histone lysine demethylases that reversibly remove methyl marks appears to challenge the epigenetic potential of histone lysine methylation. However, we argue that the reversibility of histone lysine methyl marks does not jeopardize their epigenetic status. We also suggest that not all histone lysine methylation residues are equally reversible and argue that two such residues—present exclusively in multicellular organisms—play important roles in establishing cellular identity.

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Available from: Danny Reinberg, Feb 09, 2014
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    • "Most remarkable was the absence of K9me3 in nonnucleosomal H3.1 and H3.3 (Table S1). These data imply that H3K9me3 occurs at the time of or after chromatin assembly and, if evicted, demethylation occurs immediately (Trojer and Reinberg, 2006). Given the low proportion of evicted/stored histones in our experimental conditions , H3 PTMs on nonnucleosomal complexes most likely reflect H3 status prior to incorporation into DNA. "
    Dataset: Mol Cell-06

    Full-text · Dataset · Sep 2015
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    • "(For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) whereas H3K4, H3K36 methylations have been associated with transcriptional activation and a more relaxed and open chromatin structure (Bannister and Kouzarides, 2005; Martens et al., 2005; Trojer and Reinberg, 2006; Wang et al., 2007). We have identified a significant increase in global H3K9me2 and H3K9me3 in NRK-52E cells exposed to 25, 50 and 100 lM of FB1 compared with vehicle controls. "
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    ABSTRACT: Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based food and feed. Although the effects of FB1 on sphingolipid metabolism are clear, little is known about early molecular changes associated with FB1 carcinogenicity. It has been shown that FB1 disrupts DNA methylation and chromatin modifications in HepG2 cells. We investigated dose- and time-dependent effects of FB1 in global histone modifications such as histone H3 lysine 9 di-, trimethylation (H3K9me2/me3), histone H3 lysine 4 trimethylation (H3K4me3), histone H4 lysine 20 trimethylation (H4K20me3), histone H3 lysine 9 acetylation (H3K9ac) and the enzymes involved in these mechanisms in rat kidney epithelial cells (NRK-52E). The increased levels of global H3K9me2/me3 were observed in FB1 treated cells, while the global levels of H4K20me3 and H3K9ac were decreased. FB1 caused some changes on the activities of H3K9 histone methyltransferase (HMT) and histone acetyltransferase (HAT) at high concentrations in NRK-52E cells. Further, the effects of trichostatin A (TSA), a histone deacetylase inhibitor, were investigated in NRK-52E cells. TSA was found to cause an increase on H3K9ac levels as expected. In this study we suggest that FB1 may disrupt epigenetic events by altering global histone modifications, introducing a novel aspect on the potential mechanism of FB1 carcinogenesis. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jul 2015 · Toxicology in Vitro
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    • "[29] The SMC MHC gene [26] and myocardin promoter [25] also hold KLF4 binding sites and are inhibited during SMC phenotypic switching to an inflammatory phenotype. Results of the present in vitro and in vivo experiments demonstrate that CSE-induced suppression of SMC genes was dependent on the transcription factor KLF4. Additionally, epigenetic control mechanisms including alterations in histone modifications characteristic of transcriptional suppression [39], [40], [61] provided further evidence that KLF4 regulates cerebral vascular SMC phenotypic modulation through inhibition of myocardin-mediated activation of SMC genes. [28], [62]. "
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