Back to Search
Start Over
H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation
- Source :
- PLoS Genetics, PLoS Genetics, Vol 7, Iss 3, p e1001354 (2011)
- Publication Year :
- 2011
- Publisher :
- Public Library of Science, 2011.
-
Abstract
- Methylation of histone H3 lysine 4 (H3K4me) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied. In contrast, the function of H3K4 acetylation (H3K4ac) has received little attention because of a lack of tools to separate its function from that of H3K4me. Here we show that, in addition to being methylated, H3K4 is also acetylated in budding yeast. Genetic studies reveal that the histone acetyltransferases (HATs) Gcn5 and Rtt109 contribute to H3K4 acetylation in vivo. Whilst removal of H3K4ac from euchromatin mainly requires the histone deacetylase (HDAC) Hst1, Sir2 is needed for H3K4 deacetylation in heterochomatin. Using genome-wide chromatin immunoprecipitation (ChIP), we show that H3K4ac is enriched at promoters of actively transcribed genes and located just upstream of H3K4 tri-methylation (H3K4me3), a pattern that has been conserved in human cells. We find that the Set1-containing complex (COMPASS), which promotes H3K4me2 and -me3, also serves to limit the abundance of H3K4ac at gene promoters. In addition, we identify a group of genes that have high levels of H3K4ac in their promoters and are inadequately expressed in H3-K4R, but not in set1Δ mutant strains, suggesting that H3K4ac plays a positive role in transcription. Our results reveal a novel regulatory feature of promoter-proximal chromatin, involving mutually exclusive histone modifications of the same histone residue (H3K4ac and H3K4me).<br />Author Summary In the nucleus of mammals and yeast, DNA is packaged by forming complexes with histone proteins in a structure called the nucleosome, the basic building block of chromatin. The tails of the histones protrude from the nucleosome and can be marked on many amino acid residues by chemical modifications such as methylation and acetylation. A highly studied modification, which is robustly associated with active gene promoters, is histone H3 lysine 4 methylation. We describe here a novel modification, histone H3 lysine 4 acetylation (H3K4ac), which can occur on the same lysine of the histone H3 tail (but not at the same time as methylation). We have identified the enzymes responsible for depositing and removing this mark and mapped its distribution throughout the yeast genome. We found that H3K4ac is present on active genes and is important for the full expression of a subset of them. Strikingly, H3K4 methylation was found in the same promoters as H3K4ac and contributes to regulate the abundance and localisation of H3K4ac. This example of cross-talk between two different modifications of the same residue has fundamental implications for understanding how genes are activated and how their packaging in the nucleus controls this process.
- Subjects :
- Cancer Research
Histone H3 Lysine 4
Saccharomyces cerevisiae Proteins
lcsh:QH426-470
Saccharomyces cerevisiae
Biology
Molecular Biology/Histone Modification
environment and public health
Methylation
Gene Expression Regulation, Enzymologic
Euchromatin
Histones
03 medical and health sciences
0302 clinical medicine
Sirtuin 2
Histone H1
Heterochromatin
Histone H2A
Histone methylation
Genetics
Histone code
Gene Regulatory Networks
Molecular Biology/Chromatin Structure
Promoter Regions, Genetic
Molecular Biology
Genetics (clinical)
Ecology, Evolution, Behavior and Systematics
Silent Information Regulator Proteins, Saccharomyces cerevisiae
030304 developmental biology
Histone Acetyltransferases
0303 health sciences
Lysine
Acetylation
Histone-Lysine N-Methyltransferase
Molecular Biology/Transcription Initiation and Activation
lcsh:Genetics
Biochemistry
Histone methyltransferase
Histone deacetylase
Chromatin immunoprecipitation
030217 neurology & neurosurgery
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 15537404 and 15537390
- Volume :
- 7
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics
- Accession number :
- edsair.doi.dedup.....32e65ae434fbc0eba4e4e081c079b7bc