Degree Type
Honors Capstone Project
Date of Submission
Spring 5-1-2014
Capstone Advisor
Dr. Michael Cosgrove
Honors Reader
Dr. Stephen Dorus
Capstone Major
Biology
Capstone College
Arts and Science
Audio/Visual Component
no
Capstone Prize Winner
no
Won Capstone Funding
yes
Honors Categories
Sciences and Engineering
Subject Categories
Biochemistry | Biochemistry, Biophysics, and Structural Biology
Abstract
Methylation at histone H3 lysine 4 (H3K4) is a post-translational modification often associated with transcriptional regulation through altering the structural state of chromatin. The human mixed lineage leukemia protein-1 protein (MLL1) is a known histone methyltransferase that catalyzes the transfer of methyl groups to H3K4. MLL1 works in a core complex with other essential components, proteins WDR5, RbBP5, Ash2L, DPY-30 (WRAD), which is required for H3K4 dimethylation. Trithorax (TRX) protein is the Drosophila melanogaster ortholog to human MLL1, and although structurally similar is unable to perform dimethylation when in complex with the human components. The goal of this study is to understand the structural basis for this difference. We systematically mutated 20 amino acids in TRX the equivalent amino acid in human MLL1 and tested for a gain-of-function H3K4 dimethylation activity. We found 20 amino acid positions in TRX that were highly conserved among intertebrates but were different in vertebrates. Out of the 20 amino acids mutated, 5 showed a gain of dimethylation activity. All of the mutations that showed a gain of dimethylation activity localized to a common SET domain surface. The identified mutations on the common surface identify a location of the dimethyltransferase active site on MLL1.
Recommended Citation
Monteith, Kelsey, "The Purification and Characterization of the Drosophila melanogaster Trithorax Protein and its Implications in the Studies of the SET domain Family of Proteins" (2014). Honors Capstone Projects - All. 768.
https://surface.syr.edu/honors_capstone/768
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