Active genes are tri-methylated at K4 of histone H3.

Nature 2002 Sep 11;419(6905):407-11. Epub 2002 Sep 11.

Wellcome Trust/Cancer Research UK Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK.

Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature01080DOI Listing
September 2002

Publication Analysis

Top Keywords

active genes
8
active euchromatic
8
active
5
tri-methylated defines
4
cerevisiae set1
4
set1 protein
4
presence tri-methylated
4
defines active
4
catalyse di-
4
protein catalyse
4
active state
4
silent heterochromatic
4
gene expression
4
state gene
4
heterochromatic sites
4
genes presence
4
sites saccharomyces
4
saccharomyces cerevisiae
4
exclusively active
4
euchromatic genes
4

Similar Publications

Saccharomyces cerevisiae Set1p is a methyltransferase specific for lysine 4 of histone H3 and is required for efficient gene expression.

Yeast 2003 Jul;20(9):827-35

Room 427A, Molecular Biology Building, Department of Molecular and Cellular Biology, University of Cape Town, University Private Bag, Rondebosch 7700, South Africa.

Several homologues of the Drosophila Su(var)3-9 protein were recently reported to methylate lysine 9 of histone H3. Whereas this methylation signal served to recruit heterochromatin-associated proteins to transcriptionally silenced regions, histone H3 methylated at lysine 4 was associated with transcriptionally active areas of the genome. These findings suggested that the interplay between lysine 4 and 9 methylation is crucial in eukaryotic gene regulation. Read More

View Article and Full-Text PDF
July 2003

Histone H3 lysine 4 methylation patterns in higher eukaryotic genes.

Nat Cell Biol 2004 Jan 7;6(1):73-7. Epub 2003 Dec 7.

Wellcome/CR UK Institute and Department of Pathology, Tennis Court Road, Cambridge, CB2 1QR, UK.

Lysine residues within histones can be mono-, di - or tri-methylated. In Saccharomyces cerevisiae tri-methylation of Lys 4 of histone H3 (K4/H3) correlates with transcriptional activity, but little is known about this methylation state in higher eukaryotes. Here, we examine the K4/H3 methylation pattern at the promoter and transcribed region of metazoan genes. Read More

View Article and Full-Text PDF
January 2004

Molecular regulation of histone H3 trimethylation by COMPASS and the regulation of gene expression.

Mol Cell 2005 Sep;19(6):849-56

Department of Biochemistry, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, Missouri 63104, USA.

The Set1-containing complex COMPASS, which is the yeast homolog of the human MLL complex, is required for mono-, di-, and trimethylation of lysine 4 of histone H3. We have performed a comparative global proteomic screen to better define the role of COMPASS in histone trimethylation. We report that both Cps60 and Cps40 components of COMPASS are required for proper histone H3 trimethylation, but not for proper regulation of telomere-associated gene silencing. Read More

View Article and Full-Text PDF
September 2005

Genome-wide, as opposed to local, antisilencing is mediated redundantly by the euchromatic factors Set1 and H2A.Z.

Proc Natl Acad Sci U S A 2007 Oct 9;104(42):16609-14. Epub 2007 Oct 9.

Department of Biochemistry and Biophysics, University of California, 600 16th Street, MC 2200, San Francisco, CA 94158, USA.

In Saccharomyces cerevisiae, several nonessential mechanisms including histone variant H2A.Z deposition and transcription-associated histone H3 methylation antagonize the local spread of Sir-dependent silent chromatin into adjacent euchromatic regions. However, it is unclear how and where these factors cooperate. Read More

View Article and Full-Text PDF
October 2007