Mixed Lineage Leukemia ( Mll )

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Introduction Mixed lineage leukemia (Mll) are a family of catalytic enzymes in humans which contain a highly conserved SET domain required for their full catalytic activity (Dehe et al 2015). These family of proteins are involved in regulating gene expression by methylation of the 4th Lysine residue on H3 histones. So far, 6 different types of Mll family proteins have been identified in humans one of which is Mll1 (Morgan and Shilatifard 2013). The high number of Mll subunits observed in higher Eukaryotes is believed to be the result of high demand for regulating H3K4 methylation at chromatins (Zhang et al 2015). Mll1, the most studied member of these Mll family, is an enzyme in humans coded by KMT2A gene located on chromosome 11 (Zhang et…show more content…
This demonstrates the urgency and need to study these family of proteins in effort to treat mixed lineage leukemia better. However, the large number of subunits and higher complexity of these family of proteins hinder the direct study of these proteins. Set1 is a yeast enzyme that is part of a large protein complex called COMPASS which also include Mll1 (Roguev et al 2001). Like Mll1, it also consist a highly conserved SET domain which 2 as catalytic role (Stassen et al., 1995; Laible et al., 1997). Moreover, these proteins share a similar function of regulating gene expression by mono-, di-, and tri-methylation of H3K4 (Amanika et al 2008). Thus, there exists a remarkable homology between Set1 and Mll1 proteins which allows indirect studies of Mll1 proteins. This is more ideal as Set1 is the only H3K4 methyl transferase in S.cerevisae which tremendously eliminate the complexity (Briggs et al 2001). In addition, loss of H3K4 methylation in S.cerevisae triggers apoptosis which allows better visualization of phenotypic growth differences (Walter et al 2014). Thus, studying Set1 can give important insight about Mll1 proteins and their mechanisms of action in causing leukemia. Set1 methyltransferases play an important role in gene silencing at silent chromatin regions of S.cerevisae. Silent chromatin regions are found at telomeres, HM loci (HML and HMR), and rDNA which are associated with low levels of transcription (Smith et al 1997). In previous
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