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Genome-wide patterns of histone modifications in yeast

Nature Reviews Molecular Cell Biology volume 7, pages 657–666 (2006)Cite this article

Key Points

  • The availability of antibodies that are directed against specific histone-modification sites has allowed the mapping of these sites at the whole-genome level using microarrays. Recent data in Saccharomyces cerevisiae are analysed to ask whether unique histone-modification patterns have specific functions.

  • The preferences of enzymes for particular histone sites and chromosomal locations are described. Different enzymes can affect the same genomic regions to generate unique patterns of modifications.

  • In particular, there are differences between the histone-modification patterns of heterochromatin, subtelomeric heterochromatin-adjacent regions, centromeric chromatin, promoters and coding regions. The roles of histone-modification patterns at these domains are discussed.

  • The fully deacetylated, demethylated state is necessary for repression of gene activity in heterochromatin. Domains that are partially deacetylated might be activated more easily.

  • Both acetylation and deacetylation are important for gene activity. Certain sites, including H4K16, are hypoacetylated at active genes, and histone deacetylases that deacetylate H4K16 (for example, Hos2) have also been described as activators of transcription.

  • Hypoacetylation and methylation of certain lysine residues have been shown to affect the binding of chromosomal proteins to target genes. These studies also provide a link between the methylation of a lysine residue (H3K36) and the recruitment of the histone deacetylase Rpd3 to a gene.

  • Finally, the availability of similar studies in Schizosaccharomyces pombe, which is widely divergent in evolution from S. cerevisiae, suggests that the findings above might be extrapolated to other eukaryotes.

Abstract

Post-translational histone modifications and histone variants generate complexity in chromatin to enable the many functions of the chromosome. Recent studies have mapped histone modifications across the Saccharomyces cerevisiae genome. These experiments describe how combinations of modified and unmodified states relate to each other and particularly to chromosomal landmarks that include heterochromatin, subtelomeric chromatin, centromeres, origins of replication, promoters and coding regions. Such patterns might be important for the regulation of heterochromatin-mediated silencing, chromosome segregation, DNA replication and gene expression.

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Figure 1: Known sites of histone modifications and some of the modifying enzymes in Saccharomyces cerevisiae.
Figure 2: Chromosomal domains with different combinations of histone modifications.
Figure 3: Gradients of histone methylation and acetylation in active genes.
Figure 4: Patterns of histone acetylation in Saccharomyces cerevisiae.

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Acknowledgements

The authors would like to thank members of the Grunstein laboratory and S. Kurdistani for comments on the manuscript. This work was supported by a Wellcome Trust International Research Fellowship to C.B.M. and Public Service grants Health Service grants from the National Institutes of Health to M.G.

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  1. Department of Biological Chemistry, Geffen School of Medicine and the Molecular Biology Institute, University of California, Los Angeles, 90095, California, USA

    Catherine B. Millar & Michael Grunstein

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  1. Catherine B. Millar
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DATABASES

Saccharomyces Genome Database

Abf1

Asf1

Bdf1

Bdf2

Cse4

Dot1

Eaf3

Esa1

Hda1

Hos1

Hos2

Hos3

Hst1

Hst3

Hst4

Htz1

INO1

PHO5

Rpd3

Sas2

Set1

Set2

Sir2

Sir3

Sir4

Spt10

Sum1

Ume6

FURTHER INFORMATION

Michael Grunstein's homepage

Glossary

Heterochromatin

A form of chromatin that is condensed throughout the cell cycle and is transcriptionally less active than euchromatin.

Chromatin immunoprecipitation

(ChIP). A method for determining whether a protein binds to a specific region of the genome in vivo. Live cells are treated with a crosslinking agent to form nonspecific crosslinks between the DNA and associated proteins. After shearing the chromatin into small fragments, the protein of interest is immunoprecipitated. Any protein-associated DNA is then analysed by quantitative PCR, cloning, sequencing or hybridization to microarrays (ChIP-on-chip).

Chromodomain

A conserved protein structure that is common to some chromosomal proteins. This domain interacts with chromatin by binding to methylated lysine residues in histone proteins.

WD40 domain

A 40-amino-acid protein motif that contains a WD dipeptide at its C terminus. This domain is found in many functionally diverse proteins and mediates protein–protein interactions.

Tudor domain

A domain that is related to the chromodomain and that binds methylated arginine and lysine residues.

MBT domain

A domain that is present in several transcriptional repressors that bind to methylated lysine residues.

Bromodomain

A domain that is present in many chromatin-associated proteins and that binds to acetylated lysine residues.

MYST-class HAT

A family of histone acetyltransferases that are related at the sequence level and that are named after the founding members, MOZ, Ybf2/Sas3, Sas2 and Tip60.

SIR silencing complex

A complex comprising Sir2, Sir3 and Sir4 that binds to heterochromatic regions through Sir3 and Sir4, and deacetylates histones as a result of the HDAC activity of Sir2.

Euchromatin

The non-heterochromatic portion of the genome that includes both repressed and active genes.

Hda1-affected subtelomeric (HAST) domain

Groups of contiguous genes that are deacetylated by the HDAC Hda1, and are located in the subtelomeric euchromatin.

Htz1-activated domain

(HZAD). Adjacent sub-telomeric genes, the expression of which is downregulated in the absence of the H2A variant Htz1.

Histone variant

A histone protein that differs in primary sequence from a major core histone but can substitute for it in nucleosomes.

Kinetochore

A multiprotein complex that assembles on centromeric DNA and mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.

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Millar, C., Grunstein, M. Genome-wide patterns of histone modifications in yeast. Nat Rev Mol Cell Biol 7, 657–666 (2006). https://doi.org/10.1038/nrm1986

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