Set1 Case Study

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Set1 functions as part of the multiprotein COMPASS complex that is responsible for the mono-, di-, and tri-methylation of the fourth lysine of histone 3 (H3K4) that regulates gene expression (Malik et al., 2010). COMPASS is mainly associated with the coding sequences of active genes (Shulatifard et al., 2009), therefore, the coding sequences of the actively transcribed genes are tri-methylated at H3K4 (Ng et al., 2003; Lee et al., 2007). In humans, the Mll1 protein has been linked to leukemia (Slany et al., 2009). Mll1 is the homolog of Set1 of S. cerevisiae strains and is important to gain understanding of Mll1 (Ziemin-van der Poel et al., 1991). Mutant S. Cerevisiae strains were assayed on synthetic complete media to observe
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Histones are small, positively charged proteins that interact with negative charged phosphate backbones of DNA. Double-stranded DNA loops around 8 histones (H2A, H2B, H3, and H4) twice, whilst forming the nucleosome, the building block of chromatin packaging (Van Holde et al, 1988). Histones can be modified either by acetylation, phosphorylation, methylation, or ubiquitination (Van Holde et al, 1988). Modifications of the histones collectively influence the compaction of DNA, allowing transcription to recruit histone modifiers for expression or to promote compaction for gene silencing.
Mixed lineage leukemia is characterized by the presence of MLL fusion proteins that are the result of chromosomal translocations affecting the MLL gene at 11q23 (Slany et al, 2009). The MLL complex promotes methylation. H3K4 methylation is universally introduced around the transcription at start site of all transcribed genes, and next to MLL1 several other confirmed or putative H3K4 methyltransferases (MLL2, MLL3, MLL5, MLL6 SET1A, SET1B, and ASH1L) have been identified in mammalian cells (Slany et al, 2009). Genes found to be activated in the presence of Mll1, code for factors involved in differentiation pathways, entirely in the development of mesodermal and ectodermal tissues or organogenesis cleotide pyrophosphatase, collagen type VI alpha 3(COL6A3), as well as, several hox genes
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