title: The COMPASS family of H3K4 methylases in Drosophila.
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 (lost plant homeodomains [PHDs] of Trr), 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.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Man
authors.initials: M
authors.lastname: Mohan
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Herz
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Smith
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jessica
authors.initials: J
authors.lastname: Jackson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Joel C
authors.initials: JC
authors.lastname: Eissenberg
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D017344:Genes, Insect; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D021122:Protein Subunits; D034622:RNA Interference; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D013045:Species Specificity
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; C479519:TRR protein, Drosophila