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histone methyltransferases

Wednesday 29 October 2003

DNA methylation, histone deacetylation, and methylation of histone H3 at lysine 9 are the three best-characterized covalent modifications associated with a repressed chromatin state.

Histone deacetylation and histone methylation at lysine 9 of H3 might also contribute to the establishment of DNA methylation patterns, a long-standing mystery in epigenetics.

Arginine methyltransferases

Although no arginine-specific methyltransferases have been implicated in cancer development yet, several of these enzymes are involved in gene regulatory complexes important for cell cycle regulation.

PRMT4/CARM1 positively regulates transcription of, among others, estrogen receptor-responsive genes via binding to the histone acetyl transferase CPB/p300 and methylation of Arg 17 of histone H3.

The PRMT5 arginine methyltransferase can methylate both histone H3 and H4 in vitro and interacts directly with components of the SWI/SNF complex.

PRMT5 was furthermore found to associate with and negatively regulate the cyclin E promoter. It is unknown whether methylated arginines form recognition sites for chromatin-associated proteins. Alternatively, arginine methylations may regulate other histone codes.

To this end, methylation of Arg 3 of histone H4 by PRMT1 has been found to facilitate H4 acetylation and enhance transcriptional activity. It is conceivable, therefore, that arginine methyltransferases also will display links to cancer once we learn more about these enzymes.

References

- Peters AH, Schubeler D. Methylation of histones: playing memory with DNA. Curr Opin Cell Biol. 2005 Apr;17(2):230-8. PMID: 15780602

- Fuks F. DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev. 2005 Oct;15(5):490-5. PMID: 16098738

- Huang S. Histone methyltransferases, diet nutrients and tumour suppressors. Nat Rev Cancer. 2002 Jun;2(6):469-76. PMID: 12189389

- Jenuwein T. Re-SET-ting heterochromatin by histone methyltransferases. Trends Cell Biol. 2001 Jun;11(6):266-73. PMID: 11356363