Rearrangements of the mixed lineage leukemia gene, MLL, are associated with aggressive leukemias in both children and adults. Researchers at the University of Pennsylvania School of Medicine have found that one portion of the MLL protein is an enzyme that "edits" the so-called histone code, a series of modifications to proteins associated with DNA that influence how and when certain genes are turned on and off. Their findings are presented in the November issue of Molecular Cell.
When functioning properly, the MLL protein regulates the expression of Hox genes, which play a role in cell growth and development. In some leukemias MLL is rearranged so that the cells are unable to turn off Hox genes. The Penn investigators found that a portion of the MLL protein binds directly to the Hox genes and edits the histone code at these sites. A rearranged form of MLL that causes leukemia also upregulated Hox expression but with a different "code". Presumably the differences in the pattern of histone modifications accounts for their deregulated expression in leukemia.
The histone code hypothesis was first outlined by Dr. C. David Allis and colleagues, of the University of Virginia Health System, a co-author on this paper. The theory, which rapidly is gaining acceptance, postulates that expression of certain regions of DNA is turned on and off by modifying portions of histone proteins or DNA. Modified histones and DNA attract the cells gene-reading machinery via specific interactions with these elements of the histone code.
Greg Lester | EurekAlert!
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