DNA methyltransferase Dnmt1 associates with histone deacetylase activity

@article{Fuks2000DNAMD,
  title={DNA methyltransferase Dnmt1 associates with histone deacetylase activity},
  author={François Fuks and Wendy A. Burgers and Alexander Brehm and Luke Hughes-Davies and Tony Kouzarides},
  journal={Nature Genetics},
  year={2000},
  volume={24},
  pages={88-91}
}
The DNA methyltransferase Dnmt1 is responsible for cytosine methylation in mammals and has a role in gene silencing. DNA methylation represses genes partly by recruitment of the methyl-CpG-binding protein MeCP2, which in turn recruits a histone deacetylase activity. Here we show that Dnmt1 is itself associated with histone deacetylase activity in vivo. Consistent with this association, we find that one of the known histone deacetylases, HDAC1, has the ability to bind Dnmt1 and can purify… 

Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity.

DNMT3L is a regulator of imprint establishment of normally methylated maternal genomic sequences. DNMT3L shows high similarity to the de novo DNA methyltransferases, DNMT3A and DNMT3B, however, the

SIRT1 Deacetylates the DNA Methyltransferase 1 (DNMT1) Protein and Alters Its Activities

TLDR
It is reported that the histone deacetylase SIRT1 regulates the activities of DNMT1, a key enzyme responsible for DNA methylation and is crucial forDNMT1's multiple effects in gene silencing.

The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation*

TLDR
It is shown that MeCP2 associates with histone methyltransferase activity in vivo and that this activity is directed against Lys9 of histone H3, and this activity coincides with an increase in H3 Lys9methylation.

Dnmt3L is a transcriptional repressor that recruits histone deacetylase.

TLDR
It is found that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A.

The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase.

TLDR
The data show a direct connection between the enzymes responsible for DNA methylation and histone methylation, and substantiate the notion of a self-reinforcing repressive chromatin state through the interplay between these two global epigenetic modifications.

DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci

TLDR
DNMT1 not only maintains DNA methylation, but also may directly target, in a heritable manner, transcriptionally repressive chromatin to the genome during DNA replication.

DNA methylation, nuclear structure, gene expression and cancer

TLDR
Evidence that global hypomethylation has been found in tumor samples together with cancer‐type‐specific, local hypermethylation clearly underscore the central role of DNA methylation in the regulation of gene expression and chromatin structure during normal development and diseases like cancer.

Transcriptional Repressive H3K9 and H3K27 Methylations Contribute to DNMT1-Mediated DNA Methylation Recovery

TLDR
This study has provided detailed evidence demonstrating that mammalian cells possess a bona fide DNA methylation recovery system, and it has been shown that DNAmethylation recovery was mediated by the major human DNA methyltransferase, DNMT1.

The retinoblastoma gene product interacts with maintenance human DNA (cytosine‐5) methyltransferase and modulates its activity

TLDR
Overexpression of Rb leads to hypomethylation of the cellular DNA, suggesting that Rb may modulate Dnmt1 activity during DNA replication in the cell cycle.
...

References

SHOWING 1-10 OF 30 REFERENCES

Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer

TLDR
Although DNA methylation and histone deacetylation appear to act as synergistic layers for the silencing of genes in cancer, dense CpG island methylation is dominant for the stable maintenance of a silent state at these loci.

Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex

TLDR
The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis.

Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription

TLDR
The results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.

HDAC4 deacetylase associates with and represses the MEF2 transcription factor

TLDR
It is shown that HDAC4, unlike other deacetylases, shuttles between the nucleus and the cytoplasm in a process involving active nuclear export, and suggests that compartmentalization may be a novel mechanism for controlling the nuclear activity of this new family of de acetylases.

Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.

TLDR
A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex, which may provide a means of gene silencing by DNA methylation.

DNA methylation and chromatin modification.

  • H. NgA. Bird
  • Biology, Chemistry
    Current opinion in genetics & development
  • 1999

Retinoblastoma protein recruits histone deacetylase to repress transcription

TLDR
It is shown that Rb associates with a histone deacetylase, HDAC1, through the Rb ‘pocket’ domain, and that active transcriptional repression by Rb may involve the modification of chromatin structure.

A component of the transcriptional represser MeCP1 shares a motif with DNA methyltransferase and HRX proteins

TLDR
A poly-clonal antibody raised against the protein was able to ‘supershift’ the native MeCP1 complex from HeLa cells, indicating that PCM1 is a component of mammalian MeCP2, which was expressed in bacteria and shown to bind specifically to methylated DNA.

Retinoblastoma protein represses transcription by recruiting a histone deacetylase

TLDR
It is shown here that the histone deacetylase HDAC1 physically interacts and cooperates with Rb, and that the Rb/HDAC1 complex is a key element in the control of cell proliferation and differentiation and that it is a likely target for transforming viruses.

DNA methylation represses transcription in vivo

TLDR
An embryo-specific element from the CpG island sequence upstream of Aprt is characterized that can protect itself from de novo methylation in transgenic mice as well as reduce methylation of flanking sequences.