Journal ArticleDOI
Epigenetics in human disease and prospects for epigenetic therapy
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TLDR
Great potential lies in the development of ‘epigenetic therapies’ — several inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases and histone deacetylases, have shown promising anti-tumorigenic effects for some malignancies.Abstract:
Epigenetic mechanisms, which involve DNA and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. The study of human disease has focused on genetic mechanisms, but disruption of the balance of epigenetic networks can cause several major pathologies, including cancer, syndromes involving chromosomal instabilities, and mental retardation. The development of new diagnostic tools might reveal other diseases that are caused by epigenetic alterations. Great potential lies in the development of ‘epigenetic therapies’ — several inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases and histone deacetylases, have shown promising anti-tumorigenic effects for some malignancies.read more
Citations
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Epigenetics in Cancer
TL;DR: The current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies are discussed.
Journal ArticleDOI
Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer
TL;DR: Investigating aspects of HDACi action both in vitro and in vivo will further improve the design of optimized clinical protocols and help to understand the role of histone deacetylases in tumorigenesis.
Journal ArticleDOI
Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome.
Michael Weber,Ines Hellmann,Michael B. Stadler,Liliana Ramos,Svante Pääbo,Michael Rebhan,Dirk Schübeler +6 more
TL;DR: Results show that promoter sequence and gene function are major predictors of promoter methylation states and that inactive unmethylated CpG island promoters show elevated levels of dimethylation of Lys4 of histone H3, suggesting that this chromatin mark may protect DNA from methylation.
Journal ArticleDOI
Cancer epigenomics: DNA methylomes and histone-modification maps
TL;DR: It is time to 'upgrade' cancer epigenetics research and put together an ambitious plan to tackle the many unanswered questions in this field using epigenomics approaches.
Journal ArticleDOI
The Polycomb group protein EZH2 directly controls DNA methylation
Emmanuelle Viré,Carmen Brenner,Rachel Deplus,Loïc Blanchon,Mario F. Fraga,Céline Didelot,Lluis Morey,Aleyde Van Eynde,David Bernard,Jean-Marie Vanderwinden,Mathieu Bollen,Manel Esteller,Luciano Di Croce,Yvan de Launoit,Yvan de Launoit,François Fuks +15 more
TL;DR: The results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.
References
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Journal ArticleDOI
The language of covalent histone modifications.
Brian D. Strahl,C D Allis +1 more
TL;DR: It is proposed that distinct histone modifications, on one or more tails, act sequentially or in combination to form a ‘histone code’ that is, read by other proteins to bring about distinct downstream events.
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DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.
TL;DR: It is demonstrated that two recently identified DNA methyltransferases, DnMT3a and Dnmt3b, are essential for de novo methylation and for mouse development and play important roles in normal development and disease.
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The fundamental role of epigenetic events in cancer
Peter A. Jones,Stephen B. Baylin +1 more
TL;DR: This review discusses patterns of DNA methylation and chromatin structure in neoplasia and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
Ruthie E. Amir,Ignatia B. Van den Veyver,Mimi Wan,Charles Q. Tran,Uta Francke,Huda Y. Zoghbi +5 more
TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
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Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
Xinsheng Nan,Huck-Hui Ng,Colin A. Johnson,Carol D. Laherty,Bryan M. Turner,Robert N. Eisenman,Adrian Bird +6 more
TL;DR: The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis.