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.

[1]  Steven J. M. Jones,et al.  Frequent mutation of histone modifying genes in non-Hodgkin lymphoma , 2011, Nature.

[2]  M. Ardehali,et al.  Drosophila Set1 is the major histone H3 lysine 4 trimethyltransferase with role in transcription , 2011, The EMBO journal.

[3]  A. Shilatifard,et al.  The super elongation complex (SEC) and MLL in development and disease. , 2011, Genes & development.

[4]  Zev A. Binder,et al.  The Genetic Landscape of the Childhood Cancer Medulloblastoma , 2011, Science.

[5]  B. Zhu,et al.  H3K36 Methylation Antagonizes PRC2-mediated H3K27 Methylation* , 2011, The Journal of Biological Chemistry.

[6]  R. Shiekhattar,et al.  Plant homeodomain fingers form a helping hand for transcription , 2011, Epigenetics.

[7]  A. Shilatifard,et al.  The chromatin signaling pathway: diverse mechanisms of recruitment of histone-modifying enzymes and varied biological outcomes. , 2010, Molecular cell.

[8]  Ali Shilatifard,et al.  Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis , 2010, Nature Reviews Cancer.

[9]  A. Shilatifard,et al.  Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom). , 2010, Genes & development.

[10]  A. Shilatifard,et al.  Histone H3 lysine 4 (H3K4) methylation in development and differentiation. , 2010, Developmental biology.

[11]  A. Shilatifard,et al.  The H3K27me3 Demethylase dUTX Is a Suppressor of Notch- and Rb-Dependent Tumors in Drosophila , 2010, Molecular and Cellular Biology.

[12]  M. Washburn,et al.  Refinements to label free proteome quantitation: how to deal with peptides shared by multiple proteins. , 2010, Analytical chemistry.

[13]  A. Schäffer,et al.  Distinct Genetic Alterations in Colorectal Cancer , 2010, PloS one.

[14]  M. Fang,et al.  Drosophila ptip is essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways , 2009 .

[15]  M. Fang,et al.  Drosophila ptip is essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways , 2009, Development.

[16]  G. Neri,et al.  Faculty Opinions recommendation of Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. , 2009 .

[17]  Peng Fei Wang,et al.  Molecular Regulation of H3K4 Trimethylation by Wdr82, a Component of Human Set1/COMPASS , 2008, Molecular and Cellular Biology.

[18]  Akihiko Yokoyama,et al.  Menin critically links MLL proteins with LEDGF on cancer-associated target genes. , 2008, Cancer cell.

[19]  A. Shilatifard.  Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. , 2008, Current opinion in cell biology.

[20]  J. Workman,et al.  ATAC is a double histone acetyltransferase complex that stimulates nucleosome sliding , 2008, Nature Structural &Molecular Biology.

[21]  D. Maddison,et al.  The Tree of Life Web Project , 2007 .

[22]  Laurence Florens,et al.  Histone Crosstalk between H2B Monoubiquitination and H3 Methylation Mediated by COMPASS , 2007, Cell.

[23]  Min Gyu Lee,et al.  Drosophila UTX Is a Histone H3 Lys27 Demethylase That Colocalizes with the Elongating Form of RNA Polymerase II , 2007, Molecular and Cellular Biology.

[24]  D. Skalnik,et al.  Wdr82 Is a C-Terminal Domain-Binding Protein That Recruits the Setd1A Histone H3-Lys4 Methyltransferase Complex to Transcription Start Sites of Transcribed Human Genes , 2007, Molecular and Cellular Biology.

[25]  Min Gyu Lee,et al.  Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination , 2007, Science.

[26]  G. Dressler,et al.  The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. , 2007, Developmental cell.

[27]  J. Lucchesi,et al.  A Plasmid Model System Shows that Drosophila Dosage Compensation Depends on the Global Acetylation of Histone H4 at Lysine 16 and Is Not Affected by Depletion of Common Transcription Elongation Chromatin Marks , 2007, Molecular and Cellular Biology.

[28]  D. Kioussis,et al.  Trithorax-group protein ASH1 methylates histone H3 lysine 36. , 2007, Gene.

[29]  G. Dressler,et al.  PTIP Associates with MLL3- and MLL4-containing Histone H3 Lysine 4 Methyltransferase Complex*♦ , 2007, Journal of Biological Chemistry.

[30]  D. Skalnik,et al.  Identification and Characterization of the Human Set1B Histone H3-Lys4 Methyltransferase Complex* , 2007, Journal of Biological Chemistry.

[31]  Daniel Chourrout,et al.  Genome Regulation by Polycomb and Trithorax Proteins , 2007, Cell.

[32]  T. Kouzarides.  Chromatin Modifications and Their Function , 2007, Cell.

[33]  C. Croce,et al.  Knockdown of ALR (MLL2) Reveals ALR Target Genes and Leads to Alterations in Cell Adhesion and Growth , 2006, Molecular and Cellular Biology.

[34]  John J. Wyrick,et al.  Ctk Complex-Mediated Regulation of Histone Methylation by COMPASS , 2006, Molecular and Cellular Biology.

[35]  R. Kobayashi,et al.  CUL4–DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation , 2006, Nature Cell Biology.

[36]  A. Shilatifard,et al.  Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes , 2006, Nature Structural &Molecular Biology.

[37]  Thomas A Milne,et al.  Regulation of MLL1 H3K4 methyltransferase activity by its core components , 2006, Nature Structural &Molecular Biology.

[38]  D. Skalnik,et al.  CpG-binding Protein (CXXC Finger Protein 1) Is a Component of the Mammalian Set1 Histone H3-Lys4 Methyltransferase Complex, the Analogue of the Yeast Set1/COMPASS Complex* , 2005, Journal of Biological Chemistry.

[39]  Matthew Meyerson,et al.  The Menin Tumor Suppressor Protein Is an Essential Oncogenic Cofactor for MLL-Associated Leukemogenesis , 2005, Cell.

[40]  Eric S. Lander,et al.  Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse , 2005, Cell.

[41]  W. Herr,et al.  Leukemia Proto-Oncoprotein MLL Forms a SET1-Like Histone Methyltransferase Complex with Menin To Regulate Hox Gene Expression , 2004, Molecular and Cellular Biology.

[42]  G. Kay,et al.  Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. , 2004, Molecular cell.

[43]  Lucy Cherbas,et al.  Methylation at lysine 4 of histone H3 in ecdysone-dependent development of Drosophila , 2003, Nature.

[44]  J. Lis,et al.  Transcription Factor and Polymerase Recruitment, Modification, and Movement on dhsp70 In Vivo in the Minutes following Heat Shock , 2003, Molecular and Cellular Biology.

[45]  M. Johnston,et al.  The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. , 2003, Molecular cell.

[46]  Kevin Struhl,et al.  Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. , 2003, Molecular cell.

[47]  M. Hollmann,et al.  The essential Drosophila melanogaster gene wds (will die slowly) codes for a WD-repeat protein with seven repeats , 2002, Molecular Genetics and Genomics.

[48]  Stuart L. Schreiber,et al.  Methylation of histone H3 Lys 4 in coding regions of active genes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Nevan J. Krogan,et al.  COMPASS, a Histone H3 (Lysine 4) Methyltransferase Required for Telomeric Silencing of Gene Expression* , 2002, The Journal of Biological Chemistry.

[50]  Rein Aasland,et al.  The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4 , 2001, The EMBO journal.

[51]  C. Croce,et al.  Trithorax and dCBP Acting in a Complex to Maintain Expression of a Homeotic Gene , 2001, Science.

[52]  Nevan J. Krogan,et al.  COMPASS: A complex of proteins associated with a trithorax-related SET domain protein , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[53]  F. Collins,et al.  Characterization of a MEN1 ortholog from Drosophila melanogaster. , 2001, Gene.

[54]  J. Juang,et al.  A Baculovirus Superinfection System: Efficient Vehicle for Gene Transfer into Drosophila S2 Cells , 2000, Journal of Virology.

[55]  E. Jane,et al.  The Drosophila trithorax protein binds to specific chromosomal sites and is co‐localized with Polycomb at many sites. , 1995, The EMBO journal.

[56]  W. Talbot,et al.  The drosophila EcR gene encodes an ecdysone receptor, a new member of the steroid receptor superfamily , 1991, Cell.

[57]  P. Harte,et al.  Molecular characterization of the trithorax gene, a positive regulator of homeotic gene expression in Drosophila , 1991, Mechanisms of Development.

[58]  P. Ingham,et al.  Trithorax: A new homoeotic mutation of Drosophila melanogaster causing transformations of abdominal and thoracic imaginal segments , 1980, Molecular and General Genetics MGG.

[59]  Jo Handelsman,et al.  EPIGENETIC REGULATION OF CELLULAR MEMORY BY THE POLYCOMB AND TRITHORAX GROUP PROTEINS , 2008 .

[60]  Yi Zhang,et al.  Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. , 2003, Molecular cell.

[61]  C. Wyss.  Cloning ofDrosophila cells: Effect of vitamins and yeast extract components , 1979, Somatic cell genetics.