histone methylation

Histone methylation has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity.

 Covalent modifications of histone tails have fundamental roles in chromatin structure and function. One such modification, lysine methylation, has important functions in many biological processes that include heterochromatin formation, X-chromosome inactivation and transcriptional regulation.

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

 Nucleosomal histones can be methylated in vivo at multiple residues and defined methylation patterns are related to distinct functional readouts of chromosomal DNA.

 Histone methylation has emerged as an important post-translational modification involved in transcriptional regulation and genome integrity. Recent progress in determining the cis and trans determinants of this process revealed multiple roles for histone methylation in epigenetic memory of active and silent states.

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

 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.

 Enzymes that directly remove methyl marks from histones have recently been identified, revealing a new level of plasticity within this epigenetic modification system.

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.

See also

 histone demethylases

References

 Shi Y. Histone lysine demethylases: emerging roles in development, physiology and disease. Nat Rev Genet. 2007 Nov;8(11):829-33. PMID: 17909537

 Klose RJ, Zhang Y. Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol. 2007 Apr;8(4):307-18. PMID: 17342184

 Klose RJ, Kallin EM, Zhang Y. JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet. 2006 Sep;7(9):715-27. PMID: 16983801

 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

 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

 Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49. PMID: 16261189