KANSAS CITY, MOChanges in how DNA interacts with histonesthe proteins that package DNAregulate many fundamental cell activities from stem cells maturing into a specific body cell type or blood cells becoming leukemic. These interactions are governed by a biochemical tug of war between repressors and activators, which chemically modify histones signaling them to clamp down tighter on DNA or move aside and allow a gene to be expressed.
In the November 19, 2012, online edition of the journal Genes & Development, researchers at the Stowers Institute for Medical Research report findings that may unveil the role of two human genesMLL3 and MLL4that are frequently mutated in certain cancers. In addition to its disease implications, the Stowers study exemplifies how the analysis of model organisms like yeast and fruit flies can illuminate human molecular biology.
"We know that fundamental regulatory machineries are highly conserved from yeast to Drosophila to humans," says Stowers Investigator and the study's senior author, Ali Shilatifard, Ph.D., whose lab website describes projects in yeast, fruit flies, and mammalian species. "We use the awesome power of yeast and Drosophila genetics and biochemistry to define the molecular properties of these fundamentally important factors, and then test their function in human cells. In this study, these genes turned out to be frequently mutated in several different types of cancers."
Over a decade ago, studies conducted by Shilatifard's laboratory identified an assembly of proteins known as Set1/COMPASS that biochemically modifies Histone 3 (H3) by planting methyl groups at a very precise location on the histonenamely lysine 4 (K4)within chromosomes. H3K4 can be mono-, di-, or trimethylated by Set1/COMPASS. H3K4 trimethylation by Set1/COMPASS has now become the hallmark of actively transcribed genes from yeast to human. H3K4 can also be monomethylated, and this
|Contact: Gina Kirchweger|
Stowers Institute for Medical Research