Linking the epigenetic ‘language’ of covalent histone modifications to cancer

Hake, Sandra B.; Xiao, Andrew; Allis, C. David

doi:10.1038/sj.bjc.6601575

Cited by 344 publications

(270 citation statements)

References 80 publications

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“…Methylation of nucleosomal histones occurs on lysine and arginine residues and the reaction is catalyzed by the HMTs [70]. Both the HDAC and HMT activities determine changes in the post translational modification of histone tails thus promoting the shift from a transcriptionally permissive chromatin state to a transcriptionally inactive chromatin state (reviewed in [71]) as schematically represented in Fig. 2.…”

Section: The Connection Between Dna Met Hy-lation and Other Epigenetimentioning

confidence: 99%

Dynamic and reversibility of heterochromatic gene silencing in human disease

et al. 2005

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In eukaryotic organisms cellular fate and tissue specific gene expression are regulated by the activity of proteins known as transcription factors that by interacting with specific DNA sequences direct the activation or repression of target genes. The post genomic era has shown that transcription factors are not the unique key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, post-translational modifications of histone proteins, remodeling of nucleosomes and expression of small regulatory RNAs also contribute to regulation of gene expression, determination of cell and tissue specificity and assurance of inheritance of gene expression levels. The relevant contribution of epigenetic mechanisms to a proper cellular function is highlighted by the effects of their deregulation that cooperate with genetic alterations to the development of various diseases and to the establishment and progression of tumors.

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Section: The Connection Between Dna Met Hy-lation and Other Epigenetimentioning

confidence: 99%

Dynamic and reversibility of heterochromatic gene silencing in human disease

et al. 2005

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“…[14][15][16] The levels for histone acetylation are currently believed to be controlled by the steady state balance of two classes of epigenetic enzymes, histone deacetylases (HDACs) and histone acetyltransferases. 17,18 Other than chromatin proteins, transcription factors and cell-signaling regulatory proteins could also be the substrates for HDACs. 19 Particularly, HDAC superfamily has been receiving increasing attention for its role in modulating both innate and adaptive immune responses 20,21 implicatd in allograft survival and transplantation outcome.…”

Section: Introductionmentioning

confidence: 99%

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

et al. 2012

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Suberoylanilide hydroxamic acid (SAHA), as a histone deacetylase (HDAC) inhibitor (HDACi), was recently found to exhibit an immunosuppressive effect. However, whether SAHA can synergize with calcineurin inhibitors (CNIs) to inhibit allograft rejection and its underlying mechanism remain elusive. In this study, we demonstrated the synergistic effects of SAHA and non-therapeutic dose of tacrolimus (FK506) in prolonging the allograft survival in a murine cardiac transplant model. Concomitant intragraft examination revealed that allografts from SAHA-treated recipients showed significantly lower levels of IL-17 expression, and no discernable difference for IL-17 expressions was detected between SAHA-and SAHA/FK506-treated allograft as compared with allografts from FK506-treated animals. In contrast, administration of FK506 significantly suppressed interferon (IFN)-c but increased IL-10 expression as compared with that of SAHA-treated animals, and this effect was independent of SAHA. Interestingly, SAHA synergizes with FK506 to promote Foxp3 and CTLA4 expression. In vitro, SAHA reduced the proportion of Th17 cells in isolated CD4 1 T-cell population and decreased expressions of IL-17A, IL-17F, STAT3 and RORct in these cells. Moreover, SAHA enhances suppressive function of regulatory T (Treg) cells by upregulating the expression of CTLA-4 without affecting T effector cell proliferation, and increased the proportion of Treg by selectively promoting apoptosis of T effector cells. Therefore, SAHA, a HDACi, may be a promising immunosuppressive agent with potential benefit in conjunction with CNI drugs.

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“…The association of histone proteins with DNA is affected by histone modifications that modulate the dynamic nature of chromatin fibers [48]. In general, gene expression is regulated by two components that act in concert: the binding of transcriptional activators and repressors, and the alteration of chromatin structure governed by histone modification and chromatin remodeling.…”

Section: Histone Modifications and Chromatin Remodeling In Hdmentioning

confidence: 99%

Epigenetic Mechanisms of Neurodegeneration in Huntington's Disease

et al. 2013

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Huntington's disease (HD) is an incurable and fatal hereditary neurodegenerative disorder of mid-life onset characterized by chorea, emotional distress, and progressive cognitive decline. HD is caused by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin gene. Recent studies suggest that epigenetic modifications may play a key role in HD pathogenesis. Alterations of the epigenetic "histone code" lead to chromatin remodeling and deregulation of neuronal gene transcription that are prominently linked to HD pathogenesis. Furthermore, specific noncoding RNAs and microRNAs are associated with neuronal damage in HD. In this review, we discuss how DNA methylation, posttranslational modifications of histone, and noncoding RNA function are affected and involved in HD pathogenesis. In addition, we summarize the therapeutic effects of histone deacetylase inhibitors and DNA binding drugs on epigenetic modifications and neuropathological sequelae in HD. Our understanding of the role of these epigenetic mechanisms may lead to the identification of novel biological markers and new therapeutic targets to treat HD.

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Linking the epigenetic ‘language’ of covalent histone modifications to cancer

Cited by 344 publications

References 80 publications

Dynamic and reversibility of heterochromatic gene silencing in human disease

Dynamic and reversibility of heterochromatic gene silencing in human disease

SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection

Epigenetic Mechanisms of Neurodegeneration in Huntington's Disease

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