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
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High-throughput characterization of combinatorial histone codes
Nicolas L. Young,Peter A. DiMaggio,Mariana D. Plazas-Mayorca,Richard C. Baliban,Christodoulos A. Floudas,Benjamin A. Garcia +5 more
TL;DR: A novel method utilizing “saltless” pH gradient weak cation exchange-hydrophilic interaction liquid chromatography directly coupled to electron transfer dissociation (ETD) mass spectrometry for the automated on-line high throughput characterization of hypermodified combinatorial histone codes is presented.
Journal ArticleDOI
Methylation of Histone H3 at Lysine 9 Targets Programmed DNA Elimination in Tetrahymena
TL;DR: The results extend the range of H3(Lys9)Me involvement in chromatin activities outside transcriptional regulation and also strengthen the link between heterochromatin formation and programmed DNA elimination.
Journal ArticleDOI
Do protein motifs read the histone code
Xavier de la Cruz,Sergio Lois,Sara Sánchez-Molina,Sara Sánchez-Molina,Marian A. Martínez-Balbás,Marian A. Martínez-Balbás +5 more
TL;DR: Overall, experimental evidence suggests that these domains could be involved in the recruitment of histone‐modifying enzymes to discrete chromosomal locations, and/or in the regulation their enzymatic activity.
Journal ArticleDOI
Epigenetics--an epicenter of gene regulation: histones and histone-modifying enzymes.
TL;DR: The treatment of cancer through the development of new therapies is one of the most important challenges of the authors' time, and the modulation of epigenetic mechanisms enables the alteration of cellular phenotype without altering the genotype.
Journal ArticleDOI
H2AX Is Required for Recombination Between Immunoglobulin Switch Regions but Not for Intra-Switch Region Recombination or Somatic Hypermutation
Bernardo Reina-San-Martin,Bernardo Reina-San-Martin,Simone Difilippantonio,Leif Hanitsch,Revati F. Masilamani,André Nussenzweig,Michel C. Nussenzweig,Michel C. Nussenzweig +7 more
TL;DR: It is shown that H2AX is not required for SHM, suggesting that the processing of DNA lesions leading to SHM is fundamentally different from CSR, and a role for H2 AX in regulating the higher order chromatin remodeling that facilitates switch region synapsis is suggested.
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.