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
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Heterochromatin assembly: A new twist on an old model
Peter J. Horn,Craig L. Peterson +1 more
TL;DR: Studies in the fission yeast Schizosaccharomyces pombe have begun to highlight the genetic pathways critical for the assembly and epigenetic maintenance of heterochromatin, including key roles played by the RNAi machinery, H3 lysine 9 methylation and heterochromaatin protein 1 (HP1).
Journal ArticleDOI
Meisetz and the birth of the KRAB motif
Zoë Birtle,Chris P. Ponting +1 more
TL;DR: It is shown that homologues of the histone methyltransferase Meisetz are present within the sea urchin (Strongylocentrotus purpuratus) genome, which establishes an early origin of the KRAB motif prior to the divergence of echinoderm and chordate lineages.
Journal ArticleDOI
H2B monoubiquitylation is a 5′-enriched active transcription mark and correlates with exon–intron structure in human cells
TL;DR: It is suggested that a potentiating mechanism links H2Bub1 to both H3K79 methylations in actively transcribed regions and the exon-intron structure of highly expressed exons via the regulation of nucleosome dynamics during transcription elongation.
Journal ArticleDOI
Structural Basis of H2B Ubiquitination-Dependent H3K4 Methylation by COMPASS
TL;DR: Cryoelectron microscopy structures of an extended COMPASS catalytic module (CM) bound to the H2Bub and free nucleosome are reported and establish the structural framework for understanding the long-studied H 2Bub-H3K4me histone modification crosstalk.
Journal ArticleDOI
Trypanosomatid histones: Trypanosomatid histones
Sam Alsford,David Horn +1 more
TL;DR: The presence of histone modification and variant histones in trypanosomatids represents evidence for a network that provides the discrimination required to regulate transcription, recombination, repair and chromosome replication and segregation.
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.