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Journal ArticleDOI

The language of covalent histone modifications.

Brian D. Strahl, +1 more
- 06 Jan 2000 - 
- Vol. 403, Iss: 6765, pp 41-45
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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.

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Citations
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Partitioning and Plasticity of Repressive Histone Methylation States in Mammalian Chromatin

TL;DR: The data underscore the selective presence of distinct histone lysine methylation states in partitioning chromosomal subdomains but also reveal a surprising plasticity in propagating methylation patterns in eukaryotic chromatin.
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SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins

TL;DR: KAP-1 is a molecular scaffold that is targeted by KRAB-ZFPs to specific loci and coordinates both histone methylation and the deposition of HP1 proteins to silence gene expression.
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The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription.

TL;DR: Proteomic analysis revealed that Brd4 interacts with cyclinT1 and Cdk9 that constitutes core positive transcription elongation factor b (P-TEFb) and is a positive regulatory component of P- TEFb, which alternately interacts with Brd 4 and the inhibitory subunit to maintain functional equilibrium in the cell.
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A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin

TL;DR: Together, the data indicate a function for H4-K20 trimethylation in gene silencing and further suggest H3-K9 and H4,K20 trimmedethylation as important components of a repressive pathway that can index pericentric heterochromatin.
Journal ArticleDOI

Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast

TL;DR: 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.
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.

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.
Journal ArticleDOI

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.
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