The COMPASS Family of H3K4 Methylases in Drosophila

Author:

Mohan Man1,Herz Hans-Martin1,Smith Edwin R.1,Zhang Ying1,Jackson Jessica2,Washburn Michael P.13,Florens Laurence1,Eissenberg Joel C.2,Shilatifard Ali1

Affiliation:

1. Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110

2. Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, Missouri 63104

3. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160

Abstract

ABSTRACT Methylation of histone H3 lysine 4 (H3K4) in Saccharomyces cerevisiae is implemented by Set1/COMPASS, which was originally purified based on the similarity of yeast Set1 to human MLL1 and Drosophila melanogaster Trithorax (Trx). While humans have six COMPASS family members, Drosophila possesses a representative of the three subclasses within COMPASS-like complexes: dSet1 (human SET1A/SET1B), Trx (human MLL1/2), and Trr (human MLL3/4). Here, we report the biochemical purification and molecular characterization of the Drosophila COMPASS family. We observed a one-to-one similarity in subunit composition with their mammalian counterparts, with the exception of LPT ( l ost p lant homeodomains [PHDs] of T rr), which copurifies with the Trr complex. LPT is a previously uncharacterized protein that is homologous to the multiple PHD fingers found in the N-terminal regions of mammalian MLL3/4 but not Drosophila Trr, indicating that Trr and LPT constitute a split gene of an MLL3/4 ancestor. Our study demonstrates that all three complexes in Drosophila are H3K4 methyltransferases; however, dSet1/COMPASS is the major monoubiquitination-dependent H3K4 di- and trimethylase in Drosophila . Taken together, this study provides a springboard for the functional dissection of the COMPASS family members and their role in the regulation of histone H3K4 methylation throughout development in Drosophila .

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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