Journal ArticleDOI
Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly
TLDR
In vivo evidence is provided that lysine 9 of histone H3 (H3 Lys9) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast, defining a conserved pathway wherein sequential histone modifications establish a “histone code” essential for the epigenetic inheritance of heterochROMatin assembly.Abstract:
The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys9) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SET domains of Clr4 are required for H3 Lys9 methylation in vivo. Localization of Swi6, a homolog of Drosophila HP1, to heterochomatic regions is dependent on H3 Lys9 methylation. Moreover, an H3-specific deacetylase Clr3 and a beta-propeller domain protein Rik1 are required for H3 Lys9 methylation by Clr4 and Swi6 localization. These data define a conserved pathway wherein sequential histone modifications establish a "histone code" essential for the epigenetic inheritance of heterochromatin assembly.read more
Citations
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Journal ArticleDOI
Translating the Histone Code
Thomas Jenuwein,C. David Allis +1 more
TL;DR: It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
Journal ArticleDOI
DNA methylation patterns and epigenetic memory
TL;DR: The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development.
Journal ArticleDOI
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.
Journal ArticleDOI
Gene Silencing in Cancer in Association with Promoter Hypermethylation
TL;DR: The mechanisms of gene silencing in cancer and clinical applications of this phenomenon are reviewed, especially tumor-suppressor genes.
PatentDOI
Histone demethylation mediated by the nuclear amine oxidase homolog lsd1
Yang Shi,Yujiang Shi +1 more
TL;DR: In this paper, the authors identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histonemethylases and demethylases.
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.
Journal ArticleDOI
Regulation of chromatin structure by site-specific histone H3 methyltransferases
Stephen Rea,Frank Eisenhaber,Dónal O'Carroll,Brian D. Strahl,Zu-Wen Sun,Manfred Schmid,Susanne Opravil,Karl Mechtler,Chris P. Ponting,C D Allis,Thomas Jenuwein +10 more
TL;DR: A functional interdependence of site-specific H3 tail modifications is revealed and a dynamic mechanism for the regulation of higher-order chromatin is suggested.
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Structure and ligand of a histone acetyltransferase bromodomain
TL;DR: The solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor) reveals an unusual left-handed up-and-down four-helix bundle, and it is shown by a combination of structural and site-directed mutagenesis studies that bromidomains can interact specifically with acetylated lysine, making them the first known protein modules to do so.
Journal ArticleDOI
Histone acetylation and an epigenetic code
TL;DR: Recent evidence raises the interesting possibility that an acetylation-based code may operate through both mitosis and meiosis, providing a possible mechanism for germ-line transmission of epigenetic changes.
Journal ArticleDOI
Transcriptional silencing in yeast is associated with reduced nucleosome acetylation
TL;DR: The hypothesis that silencing in yeast results from heterochromatin formation is fortified and it is argued that the silencing proteins participate in this formation.