Journal ArticleDOI
The language of covalent histone modifications.
Brian D. Strahl,C D Allis +1 more
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TLDR
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.Abstract:
Histone proteins and the nucleosomes they form with DNA are the fundamental building blocks of eukaryotic chromatin. A diverse array of post-translational modifications that often occur on tail domains of these proteins has been well documented. Although the function of these highly conserved modifications has remained elusive, converging biochemical and genetic evidence suggests functions in several chromatin-based processes. We propose 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.read more
Citations
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Mapping Global Histone Acetylation Patterns to Gene Expression
TL;DR: Certain acetylation patterns may be used as surfaces for specific protein-histone interactions, providing one mechanism for coordinate regulation of chromatin processes that are biologically related.
Journal ArticleDOI
Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9.
Peter R. Nielsen,Daniel Nietlispach,Helen R. Mott,Juliana Callaghan,Andrew J. Bannister,Tony Kouzarides,Alexey G. Murzin,Natalia V. Murzina,Ernest D. Laue +8 more
TL;DR: It is shown that HP1 uses an induced-fit mechanism for recognition of methylation of lysine 9 in histone H3, which predicts which other chromodomains will bind methylated proteins and suggest a motif that they recognize.
Journal ArticleDOI
Clinical development of histone deacetylase inhibitors as anticancer agents
Daryl C. Drummond,Charles O. Noble,Dmitri B. Kirpotin,Zexiong Guo,Gary K. Scott,Christopher C. Benz +5 more
TL;DR: An improved understanding of the mechanistic role of specific HDACs in human tumorigenesis, as well as the identification of more specificHDAC inhibitors, will likely accelerate the clinical development and broaden the future scope and utility of HDAC inhibitors for cancer treatment.
Journal ArticleDOI
Correlation Between Histone Lysine Methylation and Developmental Changes at the Chicken β-Globin Locus
TL;DR: A mechanism by which the insulator in the β-globin locus can protect the globin genes from being silenced by adjacent condensed chromatin is proposed.
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Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases.
Claudia Crosio,Gian Maria Fimia,Romain Loury,Masashi Kimura,Yukio Okano,Hongyi Zhou,Subrata Sen,C. David Allis,Paolo Sassone-Corsi +8 more
TL;DR: It is shown that the expression of Aurora-A and Aurora-B, two kinases of the Aurora/AIK family, is tightly coordinated with H3 phosphorylation during the G2/M transition, providing an attractive link between cell transformation, chromatin modifications and a specific kinase system.
References
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Journal ArticleDOI
Crystal structure of the nucleosome core particle at 2.8 Å resolution
TL;DR: The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it.
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Histone acetylation in chromatin structure and transcription
TL;DR: The amino termini of histones extend from the nucleosomal core and are modified by acetyltransferases and deacetylases during the cell cycle, which may direct histone assembly and help regulate the unfolding and activity of genes.
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Protein modules and signalling networks
TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.
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Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation.
Michael J. Hendzel,Y Wei,Michael A. Mancini,A. Van Hooser,Tamara A. Ranalli,Bill R. Brinkley,David P. Bazett-Jones,C D Allis +7 more
TL;DR: It is proposed that the singular phosphorylation of the amino-terminus of histone H3 may be involved in facilitating two key functions during mitosis: (1) regulate protein-protein interactions to promote binding of trans-acting factors that “drive” chromatin condensation as cells enter M-phase and (2) coordinate chromatin decondensation associated with M- phase.
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Histone acetylation and transcriptional regulatory mechanisms
TL;DR: Understanding of the causal relationship between histone acetylation and gene expression has been enhanced dramatically by the identification of proteins with intrinsic hist one acetylase and deacetylase activity, which led to a major paradigm shift in understanding of chromatin structure and transcription regulation.