The Methyl-CpG-binding Protein MeCP2 Links DNA Methylation to Histone Methylation*
By François Fuks, P. J. Hurd, Daniel Wolf, Xinsheng Nan, A. Bird, Tony Kouzarides. Journal of Biological Chemistry, 2003
1,046 citations recorded by the source corpus.
DNA methylation plays an important role in mammalian development and correlates with chromatin-associated gene silencing. The recruitment of MeCP2 to methylated CpG dinucleotides represents a major mechanism by which DNA methylation can repress transcription. MeCP2 silences gene expression partly by recruiting histone deacetylase (HDAC) activity, resulting in chromatin remodeling. Here, we show that MeCP2 associates with histone methyltransferase activity in vivo and that this activity is directed against Lys9 of histone H3. Two characterized repression domains of MeCP2 are involved in tethering the histone methyltransferase to MeCP2. We asked if MeCP2 can deliver Lys9 H3 methylation to the H19 gene, whose activity it represses. We show that the presence of MeCP2 on nucleosomes within the repressor region of the H19 gene (the differentially methylated domain) coincides with an increase in H3 Lys9methylation. Our data provide evidence that MeCP2 reinforces a repressive chromatin state by acting as a bridge between two global epigenetic modifications, DNA methylation and histone methylation.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/2ec3c7e18637406841fdde6730e2344fe6457ed0
How researchers see this paper
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In Genetics
- Peter A. Jones
- Manel Esteller
- Wolf Reik
- François Fuks
- W. Dean
- H. Zoghbi
- Fátima Santos
- Steven E. Jacobsen
In Molecular Biology
- Manel Esteller
- Peter A. Jones
- Wolf Reik
- François Fuks
- W. Dean
- Anna Portela
- Steven E. Jacobsen
- G. Liang
Citations in the corpus
- DNA methylation and histone modifications: teaming up to silence genes. (2005, methodology): “Biochemical data suggest that methyl-CpG-binding-domain proteins, such as MeCP2 (methyl-CpG-binding protein 2) and MBD1, might favor H3K9 methylation in the vicinity of the methylated genes that they regulate [17 ,18 ].”
- Epigenetic modifications and human disease (2010, background): “For instance, methylated DNA mediates H3K9me through MeCP2 recruitmen”
- Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome (2005, neutral): “Mecp2 associates with histone H3 Lys9 methyltransferas”
- Epigenetic gene silencing in cancer: the DNA hypermethylome. (2007, background): “Additional connections have been found: DNMTs are able also to recruit HDACs (41,42), while on the other hand, both DNMTs and MBDs recruit histone methyltransferases (HMTs) that modify lysine 9 of histone H3 (43,44).”
- Epigenetic reprogramming in mammals. (2005, background): “Conversely, in Arabidopsis, DNA methylation may also signal histone methylation, though indirect control via transcription is difficult to exclude (102), and in cultured mammalian cells, the methyl-binding domain protein MeCP2 is associated with HMTase activity (103).”
- Epigenetics in human disease and prospects for epigenetic therapy (2004, background): “Interactions between histone deacetylases (HDACs), histone methyltransferases and methylcytosine-binding protein”