Journal ArticleDOI
Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast
Zu-Wen Sun,C. David Allis +1 more
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TLDR
It is shown that the ubiquitin-conjugating enzyme Rad6 (Ubc2) mediates methylation of histone H3 at lysine 4 (Lys 4) through ubiquitination of H2B at Lys 123 in yeast (Saccharomyces cerevisiae) to reveal a pathway leading to gene regulation through concerted histone modifications on distinct histone tails.Abstract:
In eukaryotes, the DNA of the genome is packaged with histone proteins to form nucleosomal filaments, which are, in turn, folded into a series of less well understood chromatin structures. Post-translational modifications of histone tail domains modulate chromatin structure and gene expression. Of these, histone ubiquitination is poorly understood. Here we show that the ubiquitin-conjugating enzyme Rad6 (Ubc2) mediates methylation of histone H3 at lysine 4 (Lys 4) through ubiquitination of H2B at Lys 123 in yeast (Saccharomyces cerevisiae). Moreover, H3 (Lys 4) methylation is abolished in the H2B-K123R mutant, whereas H3-K4R retains H2B (Lys 123) ubiquitination. These data indicate a unidirectional regulatory pathway in which ubiquitination of H2B (Lys 123) is a prerequisite for H3 (Lys 4) methylation. We also show that an H2B-K123R mutation perturbs silencing at the telomere, providing functional links between Rad6-mediated H2B (Lys 123) ubiquitination, Set1-mediated H3 (Lys 4) methylation, and transcriptional silencing. Thus, these data reveal a pathway leading to gene regulation through concerted histone modifications on distinct histone tails. We refer to this as 'trans-tail' regulation of histone modification, a stated prediction of the histone code hypothesis.read more
Citations
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Journal ArticleDOI
Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription.
Michael J. Carrozza,Bing Li,Laurence Florens,Tamaki Suganuma,Selene K. Swanson,Kenneth K. Lee,Wei-Jong Shia,Scott Anderson,John R. Yates,Michael P. Washburn,Jerry L. Workman +10 more
TL;DR: Data indicate that Pol II-associated Set2 methylates H3 providing a transcriptional memory which signals for deacetylation of ORFs by Rpd3S, which erases transcription elongation-associated acetylation to suppress intragenic transcription initiation.
Journal ArticleDOI
Histone and chromatin cross-talk.
TL;DR: Different layers of cross-talk between several components of this complex regulatory system are emerging, and these epigenetic circuits are the focus of this review.
Journal ArticleDOI
Targeted Recruitment of Set1 Histone Methylase by Elongating Pol II Provides a Localized Mark and Memory of Recent Transcriptional Activity
TL;DR: Hypermethylated H3-K4 within the mRNA coding region persists for considerable time after transcriptional inactivation and Set1 dissociation from the chromatin, indicating that H3/K4 hypermethylation provides a molecular memory of recent transcriptional activity.
Journal ArticleDOI
Cellular Memory and the Histone Code
TL;DR: Insight is provided into how modification of one residue can influence that of another, even when they are located on different histones, and how modifications at specific genomic locations might be perpetuated on newly assembled chromatin.
Journal ArticleDOI
Chromatin Modifications by Methylation and Ubiquitination: Implications in the Regulation of Gene Expression
TL;DR: The recent biochemical, molecular, cellular, and physiological functions of histone methylation and ubiquitination involved in the regulation of gene expression as determined by a combination of enzymological, structural, and genetic methodologies are highlighted.
References
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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.
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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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Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome
Roger D. Kornberg,Yahli Lorch +1 more
TL;DR: The chromatin field needs much more information about structure beyond the nucleosome, and there is insufficient evidence that acetylation actually causes chromatin unfolding, and functional analysis in cell-free systems must be extended beyond theucleosome to the chromosomal context.
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Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails
Yi Zhang,Danny Reinberg +1 more
TL;DR: This work aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the “building blocks” of EMT and its role in cancer progression.
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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.