Acetyl-methyllysine marks chromatin at active transcription start sites
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA755299 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lysine residues in histones and other proteins can be modified by post-translational modifications (PTMs) that encode regulatory information. Lysine acetylation and methylation are especially important for regulating chromatin and gene expression. Pathways involving these PTMs are targets for clinically approved therapeutics to treat human diseases. Lysine methylation and acetylation are generally assumed to be mutually exclusive at the same residue. Here, we report the discovery of cellular lysine residues that are both methylated and acetylated on the same sidechain to form acetyl-methyllysine (Kacme). We show that Kacme is found on histone H4 across a range of species and across mammalian tissues. Kacme is associated with marks of active chromatin, increased transcriptional initiation, and is regulated in response to biological signals. H4Kacme can be installed by enzymatic acetylation of monomethyllysine peptides and is resistant to deacetylation by some HDACs in vitro. Further, Kacme can be bound by chromatin proteins that recognize modified lysine residues, as we demonstrate with the crystal structure of acetyllysine-binding protein BRD2 bound to a histone H4Kacme peptide. These results establish Kacme as a new cellular PTM with the potential to encode information distinct from methylation and acetylation alone and demonstrate that Kacme has all the hallmarks of a PTM with fundamental importance to chromatin biology.
2021-08-13 | MSV000087982 | MassIVE
Project description:Lysine residues in histones and other proteins can be modified by post-translational modifications (PTMs) that encode regulatory information. Acetylation and methylation of histone lysine residues are especially important for regulating chromatin and gene expression. Pathways involving these PTMs are targets for clinically approved therapeutics to treat human diseases. Lysine methylation and acetylation are generally assumed to be mutually exclusive at the same residue. Here, we report the discovery of cellular lysine residues that are both methylated and acetylated on the same sidechain to form acetyl-methyllysine (Kacme). We show that Kacme is found on histone H4 across a range of species and across mammalian tissues. Kacme is associated with marks of active chromatin and is regulated in response to biological signals. Analysis of nascent transcription and promoter-proximal pausing in human cells demonstrates that higher levels of Kacme are associated with higher levels of initiation and transcription. H4Kacme can be installed by enzymatic acetylation of monomethylated lysine peptides and is resistant to deacetylation by some HDACs in vitro. Further, Kacme can be bound by chromatin proteins that recognize modified lysine residues as we demonstrate with the crystal structure of acetyllysine-binding protein BRD2 bound to a histone H4Kacme peptide. These results establish Kacme as a new cellular PTM with the potential to encode information distinct from methylation and acetylation alone and demonstrate that Kacme has all the hallmarks of a PTM with fundamental importance to chromatin biology.
2023-07-21 | GSE182204 | GEO
Project description:N6-methyldeoxyadenosine (6mA or m6A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria, and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution, and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms.
2015-04-30 | GSE62690 | GEO
Project description:N6-methyldeoxyadenosine (6mA or m6A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria, and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution, and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms. Multiple sequencing methods are developed to profile the distribution of 6mA in Chlamydomonas including MeDIP-Seq, enzyme-treated DNA-Seq, MNase-Seq and RNA-Seq.
2015-04-30 | E-GEOD-62690 | biostudies-arrayexpress
Project description:N(6)-methyldeoxyadenosine (6mA or m(6)A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here, we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms.
| S-EPMC4427561 | biostudies-literature
Project description:CAGE mapping Drosophila Hemocytes start sites
| PRJEB45705 | ENA
Project description:H3K18la marks active tissue-specific enhancers
| PRJNA802354 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Our study examines the role of MMP-2 mediated Histone H3NT proteolysis in U2OS cells. We find binding of MMP-2 at all active protein coding transcription start sites, and examine the role it plays in local chromatin regulation and changes in gene expression.
2023-05-05 | GSE224887 | GEO
Project description:Our study examines the role of MMP-2 mediated Histone H3NT proteolysis in U2OS cells. We find binding of MMP-2 at all active protein coding transcription start sites, and examine the role it plays in local chromatin regulation and changes in gene expression.
2023-05-05 | GSE224886 | GEO
Project description:Our study examines the role of MMP-2 mediated Histone H3NT proteolysis in U2OS cells. We find binding of MMP-2 at all active protein coding transcription start sites, and examine the role it plays in local chromatin regulation and changes in gene expression.
2023-05-05 | GSE224885 | GEO