Errors in Erasure: Links Between Histone Lysine Methylation Removal and Disease

  • Elizabeth M. Duncan
  • C. David Allis
Part of the Progress in Drug Research book series (PDR, volume 67)


Many studies have demonstrated that covalent histone modifications are dynamically regulated to cause both chemical and physical changes to the chromatin template. Such changes in the chromatin template lead to biologically significant consequences, including differential gene expression. Histone lysine methylation, in particular, has been shown to correlate with gene expression both positively and negatively, depending on the specific site and degree (i.e., mono-, di-, or tri-) of methylation within the histone sequence. Although genetic alterations in the proteins that establish, or “write,” methyl modifications and their effect in various human pathologies have been documented, connections between the misregulation of proteins that remove, or “erase,” histone methylation and disease have emerged more recently. Here we discuss three mechanisms through which histone methylation can be removed from the chromatin template. We describe how these “erasure” mechanisms are linked to pathways that are known to be misregulated in diseases, such as cancer. We further describe how errors in the removal of histone methylation can and do lead to human pathologies, both directly and indirectly.


Esophageal Squamous Cell Carcinoma Histone Methylation Charge Syndrome Male Pronucleus Androgen Receptor Target 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Gang Wang, Ping Chi, Joanna Wysocka, and Aaron Goldberg for a critical reading of the manuscript and for helpful advice in its preparation. We apologize to all those whose work we could not cite due to space constraints. C.D.A. is supported by NIH Grant GM53512, and both C.D.A. and E.M.D. are supported by a grant from the Tri-Institutional Stem Cell Initiative (funded by the Starr Foundation).


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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Neurobiology and AnatomyUniversity of UtahSalt Lake CityUSA

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