Trithorax group proteins: switching genes on and keeping them active

Cellular memory is provided by two counteracting groups of chromatin proteins termed Trithorax group (TrxG) and Polycomb group (PcG) proteins. TrxG proteins activate transcription and are perhaps best known because of the involvement of the TrxG protein MLL in leukaemia. However, in terms of molecular analysis, they have lived in the shadow of their more famous counterparts, the PcG proteins. Recent advances have improved our understanding of TrxG protein function and demonstrated that the heterogeneous group of TrxG proteins is of critical importance in the epigenetic regulation of the cell cycle, senescence, DNA damage and stem cell biology.

[1]  T. Golub,et al.  Conditional MLL‐CBP targets GMP and models therapy‐related myeloproliferative disease , 2005, The EMBO journal.

[2]  T. Graeber,et al.  An integrated approach to dissecting oncogene addiction implicates a Myb-coordinated self-renewal program as essential for leukemia maintenance. , 2011, Genes & development.

[3]  B. Meyer,et al.  An MLL/COMPASS subunit functions in the C. elegans dosage compensation complex to target X chromosomes for transcriptional regulation of gene expression. , 2011, Genes & Development.

[4]  T. Derrien,et al.  Long Noncoding RNAs with Enhancer-like Function in Human Cells , 2010, Cell.

[5]  M. Leeb,et al.  The Trithorax group protein Ash2l and Saf-A are recruited to the inactive X chromosome at the onset of stable X inactivation , 2010, Development.

[6]  A. F. Stewart,et al.  Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase Mll2. , 2007, Molecular biology of the cell.

[7]  A. Shilatifard,et al.  Parafibromin, a Component of the Human PAF Complex, Regulates Growth Factors and Is Required for Embryonic Development and Survival in Adult Mice , 2008, Molecular and Cellular Biology.

[8]  A. Tarakhovsky,et al.  Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex , 2010, Proceedings of the National Academy of Sciences.

[9]  M. Yaniv,et al.  The hbrm and BRG‐1 proteins, components of the human SNF/SWI complex, are phosphorylated and excluded from the condensed chromosomes during mitosis. , 1996, The EMBO journal.

[10]  Dustin E. Schones,et al.  Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. , 2009, Cell stem cell.

[11]  G. Fan,et al.  Epigenetic Regulation of Neural Gene Expression and Neuronal Function , 2007, Pediatric Research.

[12]  Kristian Helin,et al.  The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells. , 2007, Genes & development.

[13]  Y. Kotake,et al.  DDB1-CUL4 and MLL1 mediate oncogene-induced p16INK4a activation. , 2009, Cancer research.

[14]  S. Khorasanizadeh,et al.  Double chromodomains cooperate to recognize the methylated histone H3 tail , 2005, Nature.

[15]  Martin J. Walsh,et al.  Fgfr3 Is a Transcriptional Target of Ap2δ and Ash2l-Containing Histone Methyltransferase Complexes , 2009, PloS one.

[16]  A. D’Andrea,et al.  Menin associates with FANCD2, a protein involved in repair of DNA damage. , 2003, Cancer research.

[17]  D. Carrasco,et al.  Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis , 2001, Nature.

[18]  Renato Paro,et al.  A combined ex vivo and in vivo RNAi screen for notch regulators in Drosophila reveals an extensive notch interaction network. , 2010, Developmental cell.

[19]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[20]  Winship Herr,et al.  E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. , 2007, Molecular cell.

[21]  J. Zuber,et al.  A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit. , 2009, Molecular cell.

[22]  H. Vogel,et al.  CHD5 Is a Tumor Suppressor at Human 1p36 , 2007, Cell.

[23]  G. Lyons,et al.  The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. , 2004, Genes & development.

[24]  F. Collins,et al.  A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[25]  N. Killeen,et al.  MLL5 contributes to hematopoietic stem cell fitness and homeostasis. , 2009, Blood.

[26]  C. Doe,et al.  Genetic Screens for Enhancers of brahma Reveal Functional Interactions Between the BRM Chromatin-Remodeling Complex and the Delta-Notch Signal Transduction Pathway in Drosophila , 2005, Genetics.

[27]  C. Simone,et al.  p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci , 2004, Nature Genetics.

[28]  Molly C. Kottemann,et al.  Characterization of DNA damage-dependent cell cycle checkpoints in a menin-deficient model. , 2009, DNA repair.

[29]  Thomas A. Milne,et al.  WDR5 Associates with Histone H3 Methylated at K4 and Is Essential for H3 K4 Methylation and Vertebrate Development , 2005, Cell.

[30]  Jon R. Wilson,et al.  Methylation and demethylation activities of a C. elegans MLL-like complex attenuate RAS signalling. , 2010, Developmental biology.

[31]  Giacomo Cavalli,et al.  Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling , 2009, Nature Genetics.

[32]  Y. Kotake,et al.  pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. , 2007, Genes & development.

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

[34]  G. Schubiger,et al.  Regulation of cellular plasticity in Drosophila imaginal disc cells by the Polycomb group, trithorax group and lama genes , 2005, Development.

[35]  S. Sabatini,et al.  The CHD3 Chromatin Remodeler PICKLE and Polycomb Group Proteins Antagonistically Regulate Meristem Activity in the Arabidopsis Root[C][W] , 2011, Plant Cell.

[36]  E. Greer,et al.  Transgenerational Epigenetic Inheritance of Longevity in C. elegans , 2011, Nature.

[37]  Giacomo Cavalli,et al.  Recruitment of Polycomb group complexes and their role in the dynamic regulation of cell fate choice , 2009, Development.

[38]  Jeffrey L. Wrana,et al.  Baf60c is essential for function of BAF chromatin remodelling complexes in heart development , 2004, Nature.

[39]  A. Shilatifard,et al.  Drosophila Rtf1 functions in histone methylation, gene expression, and Notch signaling , 2006, Proceedings of the National Academy of Sciences.

[40]  Benjamin L. Kidder,et al.  SWI/SNF‐Brg1 Regulates Self‐Renewal and Occupies Core Pluripotency‐Related Genes in Embryonic Stem Cells , 2009, Stem cells.

[41]  J. Davie,et al.  Promoter chromatin remodeling of immediate-early genes is mediated through H3 phosphorylation at either serine 28 or 10 by the MSK1 multi-protein complex , 2010, Nucleic acids research.

[42]  C. Allis,et al.  Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. , 2010, Molecular cell.

[43]  Juri Rappsilber,et al.  A model for transmission of the H3K27me3 epigenetic mark , 2008, Nature Cell Biology.

[44]  G. Crabtree,et al.  Chromatin remodelling during development , 2010, Nature.

[45]  C. Mello,et al.  MEP-1 and a Homolog of the NURD Complex Component Mi-2 Act Together to Maintain Germline-Soma Distinctions in C. elegans , 2002, Cell.

[46]  H. Korswagen,et al.  Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells , 2011, Proceedings of the National Academy of Sciences.

[47]  X. Hua,et al.  In search of tumor suppressing functions of menin , 2007, Molecular and Cellular Endocrinology.

[48]  S. Méresse,et al.  Histone and DNA methylation defects at Hox genes in mice expressing a SET domain-truncated form of Mll. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

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

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

[51]  Jürg Müller,et al.  Histone trimethylation and the maintenance of transcriptional ON and OFF states by trxG and PcG proteins. , 2006, Genes & development.

[52]  Yali Dou,et al.  Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases , 2006, Proceedings of the National Academy of Sciences.

[53]  H. Ng,et al.  T‐Cell Factor 3 Regulates Embryonic Stem Cell Pluripotency and Self‐Renewal by the Transcriptional Control of Multiple Lineage Pathways , 2008, Stem cells.

[54]  E. O’Shea,et al.  Regulation of Chromatin Remodeling by Inositol Polyphosphates , 2002, Science.

[55]  M. Yaniv,et al.  The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression , 2000, EMBO reports.

[56]  M. Brand,et al.  Crystal structure of the trithorax group protein Ash2L reveals a Forkhead-like DNA binding domain , 2011, Nature Structural &Molecular Biology.

[57]  E. Greer,et al.  Members of the H 3 K 4 trimethylation complex regulate lifespan in a germline-dependent manner in C . elegans , 2010 .

[58]  S. Mandal,et al.  Mixed lineage leukemia: roles in gene expression, hormone signaling and mRNA processing , 2010, The FEBS journal.

[59]  B. Emerson,et al.  Transcriptional specificity of human SWI/SNF BRG1 and BRM chromatin remodeling complexes. , 2003, Molecular cell.

[60]  R. Dulermo,et al.  Antagonistic functions of SET-2/SET1 and HPL/HP1 proteins in C. elegans development. , 2007, Developmental biology.

[61]  E. Green,et al.  MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia , 2002, Oncogene.

[62]  A. F. Stewart,et al.  The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis , 2009, Epigenetics & Chromatin.

[63]  Jiaying Tan,et al.  The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. , 2010, Cancer cell.

[64]  Yves Levy,et al.  HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP. , 2010, Molecular cell.

[65]  A. Bale,et al.  Multiple Endocrine Neoplasia Type 1 (MEN1) as a Cancer Predisposition Syndrome: Clues into the Mechanisms of MEN1-related Carcinogenesis , 2006, The Yale journal of biology and medicine.

[66]  R. Siebert,et al.  Inv(11)(q21q23) fuses MLL to the Notch co-activator mastermind-like 2 in secondary T-cell acute lymphoblastic leukemia , 2008, Leukemia.

[67]  Sheryl T. Smith,et al.  Association of trxG and PcG proteins with the bxd maintenance element depends on transcriptional activity , 2008, Development.

[68]  H. Alder,et al.  The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene , 1992, Cell.

[69]  Michael B. Stadler,et al.  Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. , 2008, Molecular cell.

[70]  J. B. Jaynes,et al.  Transcription of bxd Noncoding RNAs Promoted by Trithorax Represses Ubx in cis by Transcriptional Interference , 2006, Cell.

[71]  G. Davies,et al.  Knowns and Unknowns , 2003 .

[72]  Todd D. Westergard,et al.  Phosphorylation of MLL by ATR is Required for Execution of Mammalian S Phase Checkpoint , 2010, Nature.

[73]  Ying E. Zhang,et al.  Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells , 2008, PLoS genetics.

[74]  P. Ingham Differential expression of bithorax complex genes in the absence of the extra sex combs and trithorax genes , 1983, Nature.

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

[76]  Robert S. Illingworth,et al.  CpG islands influence chromatin structure via the CpG-binding protein Cfp1 , 2010, Nature.

[77]  Bradley E. Bernstein,et al.  GC-Rich Sequence Elements Recruit PRC2 in Mammalian ES Cells , 2010, PLoS genetics.

[78]  M. Milán,et al.  Genetic and epigenetic mechanisms regulating hedgehog expression in the Drosophila wing. , 2009, Developmental biology.

[79]  Michael T. McManus,et al.  Chd1 regulates open chromatin and pluripotency of embryonic stem cells , 2009, Nature.

[80]  Keesook Lee,et al.  Srg3, a Mouse Homolog of Yeast SWI3, Is Essential for Early Embryogenesis and Involved in Brain Development , 2001, Molecular and Cellular Biology.

[81]  S. Henikoff,et al.  Genome-Wide Kinetics of Nucleosome Turnover Determined by Metabolic Labeling of Histones , 2010, Science.

[82]  F. Collins,et al.  The 32-Kilodalton Subunit of Replication Protein A Interacts with Menin, the Product of the MEN1 Tumor Suppressor Gene , 2003, Molecular and Cellular Biology.

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

[84]  W. Zong,et al.  Menin Induces Apoptosis in Murine Embryonic Fibroblasts* , 2004, Journal of Biological Chemistry.

[85]  E. Guccione,et al.  Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive , 2007, Nature.

[86]  A. Brehm,et al.  ATP-dependent chromatin remodeling complexes in Drosophila , 2006, Chromosome Research.

[87]  P. Ingham trithorax and the regulation of homeotic gene expression in Drosophila: a historical perspective. , 1998, The International journal of developmental biology.

[88]  H. Masai,et al.  Functional Interaction between Tumor Suppressor Menin and Activator of S-Phase Kinase , 2004, Cancer Research.

[89]  Tilman Sanchez-Elsner,et al.  Noncoding RNAs of Trithorax Response Elements Recruit Drosophila Ash1 to Ultrabithorax , 2006, Science.

[90]  A. Shilatifard,et al.  A comprehensive library of histone mutants identifies nucleosomal residues required for H3K4 methylation , 2008, Nature Structural &Molecular Biology.

[91]  Y. Hayashi,et al.  Identification of a novel fusion gene MLL‐MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23) , 2007, Genes, chromosomes & cancer.

[92]  W. G. Kelly,et al.  A Role for Set1/MLL-Related Components in Epigenetic Regulation of the Caenorhabditis elegans Germ Line , 2011, PLoS genetics.

[93]  M. Kirschner,et al.  Mitotic inactivation of a human SWI/SNF chromatin remodeling complex. , 1998, Genes & development.

[94]  R. Paro,et al.  Epigenetic inheritance of active chromatin after removal of the main transactivator. , 1999, Science.

[95]  K. Basler,et al.  The ISWI‐containing NURF complex regulates the output of the canonical Wingless pathway , 2009, EMBO reports.

[96]  S. Korsmeyer,et al.  Taspase1 A Threonine Aspartase Required for Cleavage of MLL and Proper HOX Gene Expression , 2003, Cell.

[97]  Guo-Cheng Yuan,et al.  Prediction of Polycomb target genes in mouse embryonic stem cells. , 2010, Genomics.

[98]  G. Natoli,et al.  The Histone H3 Lysine 27-Specific Demethylase Jmjd3 Is Required for Neural Commitment , 2008, PloS one.

[99]  O. Rozenblatt-Rosen,et al.  Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27Kip1 and p18INK4c. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[100]  Todd D. Westergard,et al.  Proteolysis of MLL Family Proteins Is Essential for Taspase1−Orchestrated Cell Cycle Progression. , 2006 .

[101]  Enrique Blanco,et al.  Genome-wide chromatin occupancy analysis reveals a role for ASH2 in transcriptional pausing , 2011, Nucleic acids research.

[102]  O. Rozenblatt-Rosen,et al.  Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[103]  Y. Sancak,et al.  Tissue-Specific TAFs Counteract Polycomb to Turn on Terminal Differentiation , 2005, Science.

[104]  Han Liu,et al.  Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions. , 2007, Genes & development.

[105]  Robert E. Kingston,et al.  Mechanisms of Polycomb gene silencing: knowns and unknowns , 2009, Nature Reviews Molecular Cell Biology.

[106]  P. Cheung,et al.  Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing , 2011, Proceedings of the National Academy of Sciences.

[107]  R. Eisenman,et al.  The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth. , 2007, Genes & development.

[108]  C. Verrijzer,et al.  SWI/SNF Mediates Polycomb Eviction and Epigenetic Reprogramming of the INK4b-ARF-INK4a Locus , 2008, Molecular and Cellular Biology.

[109]  Per Stenberg,et al.  Alternative Epigenetic Chromatin States of Polycomb Target Genes , 2010, PLoS genetics.

[110]  E. Wieschaus,et al.  Coordinated regulation of Myc trans-activation targets by Polycomb and the Trithorax group protein Ash1 , 2007, BMC Molecular Biology.

[111]  A. Shilatifard,et al.  RAD6-Mediated Transcription-Coupled H2B Ubiquitylation Directly Stimulates H3K4 Methylation in Human Cells , 2009, Cell.

[112]  G. Valk,et al.  Multiple Endocrine Neoplasia Type 1 (MEN 1) , 2009 .

[113]  Role for Dpy-30 in ES Cell-Fate Specification by Regulation of H3K4 Methylation within Bivalent Domains , 2011, Cell.

[114]  M. Fritsch,et al.  High Histone Acetylation and Decreased Polycomb Repressive Complex 2 Member Levels Regulate Gene Specific Transcriptional Changes During Early Embryonic Stem Cell Differentiation Induced by Retinoic Acid , 2007, Stem cells.

[115]  A. Berns,et al.  Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice , 2001, Nature.

[116]  S. Tapscott,et al.  p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation , 2007, Nature Structural &Molecular Biology.

[117]  J. Treisman,et al.  Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13 , 2008, Proceedings of the National Academy of Sciences.

[118]  Jürg Bähler,et al.  Arginine methylation at histone H3R2 controls deposition of H3K4 trimethylation , 2007, Nature.

[119]  P. Meltzer,et al.  Activating Signal Cointegrator 2 Belongs to a Novel Steady-State Complex That Contains a Subset of Trithorax Group Proteins , 2003, Molecular and Cellular Biology.

[120]  T. Mikkelsen,et al.  Genome-wide maps of chromatin state in pluripotent and lineage-committed cells , 2007, Nature.

[121]  M. Blasco,et al.  Cellular Senescence in Cancer and Aging , 2007, Cell.

[122]  G. Pan,et al.  Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. , 2007, Cell stem cell.

[123]  Jürg Müller,et al.  The histone methyltransferases Trithorax and Ash1 prevent transcriptional silencing by Polycomb group proteins , 2004, EMBO reports.

[124]  M. Cole,et al.  Transcriptional activation by the Myc oncoprotein. , 2006, Current topics in microbiology and immunology.

[125]  Giacomo Cavalli,et al.  Chromatin inheritance upon Zeste‐mediated Brahma recruitment at a minimal cellular memory module , 2004, The EMBO journal.

[126]  E. Olson,et al.  Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development , 2009, Proceedings of the National Academy of Sciences.

[127]  M. Scott,et al.  The Drosophila BRM complex facilitates global transcription by RNA polymerase II , 2002, The EMBO journal.

[128]  Howard Y. Chang,et al.  A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression , 2011, Nature.

[129]  S. Korsmeyer,et al.  Altered Hox expression and segmental identity in Mll-mutant mice , 1995, Nature.

[130]  D. Kioussis,et al.  Mll has a critical role in fetal and adult hematopoietic stem cell self-renewal. , 2007, Cell stem cell.

[131]  Jonathan M. Monk,et al.  Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network , 2011, Cell.

[132]  Juri Rappsilber,et al.  JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells , 2010, Nature.

[133]  S. Orkin,et al.  An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells , 2008, Cell.

[134]  Thomas A. Milne,et al.  A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling , 2006, Nature.

[135]  S. G. Cheng,et al.  c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transactivation function , 1999, Nature Genetics.

[136]  Ryan A. Flynn,et al.  A unique chromatin signature uncovers early developmental enhancers in humans , 2011, Nature.

[137]  W. Herr,et al.  E2F1 mediates DNA damage and apoptosis through HCF‐1 and the MLL family of histone methyltransferases , 2009, The EMBO journal.

[138]  Matthias Mann,et al.  Selective Anchoring of TFIID to Nucleosomes by Trimethylation of Histone H3 Lysine 4 , 2007, Cell.

[139]  A. Shilatifard,et al.  The COMPASS Family of H3K4 Methylases in Drosophila , 2011, Molecular and Cellular Biology.

[140]  Y. Dou,et al.  PRMT6-mediated methylation of R2 in histone H3 antagonizes H3 K4 trimethylation. , 2007, Genes & development.

[141]  N. Sharpless,et al.  The Regulation of INK4/ARF in Cancer and Aging , 2006, Cell.

[142]  P. Ernst,et al.  Developmentally-induced Mll1 loss reveals defects in postnatal haematopoiesis , 2010, Leukemia.

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

[144]  Thomas A. Milne,et al.  Recognition of a Mononucleosomal Histone Modification Pattern by BPTF via Multivalent Interactions , 2011, Cell.

[145]  M. Akam,et al.  The molecular basis for metameric pattern in the Drosophila embryo. , 1987, Development.

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

[147]  N. D. Clarke,et al.  Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem Cells , 2008, Cell.

[148]  Z. Avramova Evolution and pleiotropy of TRITHORAX function in Arabidopsis. , 2009, The International journal of developmental biology.

[149]  Sean Davis,et al.  Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis , 2006, PLoS genetics.

[150]  Han Liu,et al.  Biphasic MLL takes helm at cell cycle control: Implications in human mixed lineage leukemia , 2008, Cell cycle.

[151]  G. Pavlath,et al.  MLL5, a trithorax homolog, indirectly regulates H3K4 methylation, represses cyclin A2 expression, and promotes myogenic differentiation , 2009, Proceedings of the National Academy of Sciences.

[152]  Dustin E. Schones,et al.  Genome-wide Mapping of HATs and HDACs Reveals Distinct Functions in Active and Inactive Genes , 2009, Cell.

[153]  R. Paro,et al.  Expression of leukemic MLL fusion proteins in Drosophila affects cell cycle control and chromosome morphology , 2004, Oncogene.

[154]  V. Avvedimento,et al.  Menin stimulates homology‐directed DNA repair , 2010, FEBS letters.

[155]  W. Herr Faculty Opinions recommendation of Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression. , 2004 .

[156]  J. Kennison,et al.  Dosage-dependent modifiers of polycomb and antennapedia mutations in Drosophila. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[157]  D. Reinberg,et al.  Role of the polycomb protein EED in the propagation of repressive histone marks , 2009, Nature.

[158]  R. Tjian,et al.  ES cell pluripotency and germ-layer formation require the SWI/SNF chromatin remodeling component BAF250a , 2008, Proceedings of the National Academy of Sciences.

[159]  J. Chayvialle,et al.  Reduction of Menin Expression Enhances Cell Proliferation and Is Tumorigenic in Intestinal Epithelial Cells* , 2004, Journal of Biological Chemistry.

[160]  K. Döhner,et al.  Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog MLL5. , 2009, Blood.

[161]  Martin M. Matzuk,et al.  MLL2 Is Required in Oocytes for Bulk Histone 3 Lysine 4 Trimethylation and Transcriptional Silencing , 2010, PLoS biology.

[162]  N. Zeleznik-Le,et al.  The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[163]  Michael L. Cleary,et al.  Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias , 1992, Cell.

[164]  Rakhee Banerjee,et al.  Polycomb Repressive Complex 2 and Trithorax modulate Drosophila longevity and stress resistance , 2009, Proceedings of the National Academy of Sciences.

[165]  K. Helin,et al.  Polycomb group protein displacement and gene activation through MSK-dependent H3K27me3S28 phosphorylation. , 2010, Molecular cell.

[166]  G. Crawford,et al.  Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. , 2009, Genome research.

[167]  Radu Dobrin,et al.  Dissecting self-renewal in stem cells with RNA interference , 2006, Nature.

[168]  G. Pavlath,et al.  A gene-trap strategy identifies quiescence-induced genes in synchronized myoblasts , 2008, Journal of Biosciences.

[169]  Thomas A. Milne,et al.  Physical Association and Coordinate Function of the H3 K4 Methyltransferase MLL1 and the H4 K16 Acetyltransferase MOF , 2005, Cell.

[170]  J. Goodliffe,et al.  Su(z)2 Antagonizes Auto-Repression of Myc in Drosophila, Increasing Myc Levels and Subsequent Trans-Activation , 2009, PloS one.

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

[172]  R. Goodman,et al.  Functional Interaction between the CoactivatorDrosophila CREB-Binding Protein and ASH1, a Member of the Trithorax Group of Chromatin Modifiers , 2000, Molecular and Cellular Biology.

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

[174]  A. Shilatifard,et al.  AFF4, a component of the ELL/P-TEFb elongation complex and a shared subunit of MLL chimeras, can link transcription elongation to leukemia. , 2010, Molecular cell.

[175]  S. Asli Özgün-Koca,et al.  A Historical Perspective from "a" to "c" , 2010 .

[176]  Wei-Hua Wu,et al.  Modulation of ATP-Dependent Chromatin-Remodeling Complexes by Inositol Polyphosphates , 2002, Science.

[177]  R. Tjian,et al.  The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila innate immunity. , 2008, Developmental biology.

[178]  F Randazzo,et al.  A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. , 2000, Molecular cell.

[179]  E. Lewis A gene complex controlling segmentation in Drosophila , 1978, Nature.

[180]  Diletta Dolfini,et al.  NF-Y Recruits Ash2L to Impart H3K4 Trimethylation on CCAAT Promoters , 2011, PloS one.

[181]  Edwin Smith,et al.  The Language of Histone Crosstalk , 2010, Cell.

[182]  Ruedi Aebersold,et al.  Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus. , 2007, Molecular cell.

[183]  F. Winston,et al.  Yeast SNF/SWI transcriptional activators and the SPT/SIN chromatin connection. , 1992, Trends in genetics : TIG.

[184]  Mikael Sigvardsson,et al.  Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells. , 2010, Blood.

[185]  Bin Tean Teh,et al.  Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer , 2009, Nature Genetics.

[186]  H Clevers,et al.  The chromatin remodelling factor Brg‐1 interacts with β‐catenin to promote target gene activation , 2001, The EMBO journal.

[187]  A. Nagel,et al.  The Putzig-NURF Nucleosome Remodeling Complex Is Required for Ecdysone Receptor Signaling and Innate Immunity in Drosophila melanogaster , 2011, Genetics.

[188]  M. Cleary,et al.  A higher-order complex containing AF4 and ENL family proteins with P-TEFb facilitates oncogenic and physiologic MLL-dependent transcription. , 2010, Cancer cell.

[189]  Keji Zhao,et al.  An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network , 2009, Proceedings of the National Academy of Sciences.

[190]  A. Fisher,et al.  Chromatin states in pluripotent, differentiated, and reprogrammed cells. , 2011, Current opinion in genetics & development.

[191]  Hisashi Tanaka,et al.  Gene Regulation and Epigenetic Remodeling in Murine Embryonic Stem Cells by c-Myc , 2009, PloS one.

[192]  P. Scacheri,et al.  CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing , 2009, Development.

[193]  S. Aparicio,et al.  Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. , 2009, Blood.

[194]  R. Paro,et al.  Intergenic transcription through a polycomb group response element counteracts silencing. , 2005, Genes & development.

[195]  J. Tamkun,et al.  Drosophila Kismet Regulates Histone H3 Lysine 27 Methylation and Early Elongation by RNA Polymerase II , 2008, PLoS genetics.