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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Journal ArticleDOI
Histone Modifications and the Maintenance of Telomere Integrity
Meagan Jezek,Erin M. Green +1 more
TL;DR: Current knowledge regarding the role of histone modifications in maintaining telomeric and subtelomeric chromatin is reviewed, the implications of hist one modification marks as they relate to human disease are discussed, and key areas for future research are highlighted.
Journal ArticleDOI
The ubiquitin-proteasome system in prostate cancer and its transition to castration resistance.
TL;DR: The role of ubiquitin-proteasome system (UPS) in androgen receptor-dependent transcription as well as in the castration resistant stage of the disease, and the therapeutic opportunities that UPS inhibition offers in prostate cancer are discussed.
Journal ArticleDOI
The Set1 N-terminal Domain and Swd2 Interact With RNA Polymerase II CTD to Recruit COMPASS
Hyun Jin Bae,Marion Dubarry,Jongcheol Jeon,Jongcheol Jeon,Luis M. Soares,Catherine Dargemont,Jae-Hoon Kim,Vincent Géli,Stephen Buratowski +8 more
TL;DR: Evidence is provided that the Set1 N-terminal region and the COMPASS subunit Swd2 interact with RNA polymerase II CTD to recruit COMPASS in budding yeast to establish proper levels and distribution of H3K4 methylations.
Book ChapterDOI
Global proteomic analysis of S. cerevisiae (GPS) to identify proteins required for histone modifications.
Journal ArticleDOI
Epigenetic dysfunctional diseases and therapy for infection and inflammation.
TL;DR: It is important to understand the epigenetic machinery and the function of its components in specific diseases to develop targeted epigenetic therapy and it is equally critical to know the specific inhibitors other than the widely used pan inhibitors in clinical trials and explore their roles in regulating specific genes in a more defined way during infection.
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.
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
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.
Journal ArticleDOI
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.
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.