Targeting epigenetic readers in cancer.

Much of gene expression is regulated by chromatin, which allows or blocks transcription. Alterations in chromatin that influence gene expression in certain cancers can be affected by drugs. Clinical testing is eagerly awaited.

[1]  Anjanabha Saha,et al.  ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression , 2006, Nature.

[2]  J. Rowley.  Chromosomal translocations: revisited yet again. , 2008, Blood.

[3]  A. Tefferi,et al.  Myelodysplastic syndromes. , 2009, The New England journal of medicine.

[4]  B. Löwenberg,et al.  A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects. , 2009, Blood.

[5]  R. Young,et al.  BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc , 2011, Cell.

[6]  Mark A. Dawson,et al.  Inhibition of BET Recruitment to Chromatin As An Effective Treatment for MLL-Fusion Leukaemia , 2011 .

[7]  R. Kornberg,et al.  Mammalian mediator of transcriptional regulation and its possible role as an end-point of signal transduction pathways. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Shilatifard,et al.  An operational definition of epigenetics. , 2009, Genes & development.

[9]  J. Vose,et al.  Peripheral T-cell lymphoma. , 2011, Blood.

[10]  C. Bach,et al.  Misguided Transcriptional Elongation Causes Mixed Lineage Leukemia , 2009, PLoS biology.

[11]  Xiangyuan Wang,et al.  Double bromodomain‐containing gene Brd2 is essential for embryonic development in mouse , 2009, Developmental dynamics : an official publication of the American Association of Anatomists.

[12]  Peter A. Jones,et al.  A decade of exploring the cancer epigenome — biological and translational implications , 2011, Nature Reviews Cancer.

[13]  Dinshaw J. Patel,et al.  Multivalent engagement of chromatin modifications by linked binding modules , 2007, Nature Reviews Molecular Cell Biology.

[14]  Lei Zeng,et al.  Structure and ligand of a histone acetyltransferase bromodomain , 1999, Nature.

[15]  L. Penn,et al.  Reflecting on 25 years with MYC , 2008, Nature Reviews Cancer.

[16]  C. Rice,et al.  Suppression of inflammation by a synthetic histone mimic , 2010, Nature.

[17]  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.

[18]  Youngchang Kim,et al.  Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. , 2003, Genes & development.

[19]  C. Chiang,et al.  Brd4 engagement from chromatin targeting to transcriptional regulation: selective contact with acetylated histone H3 and H4 , 2009, F1000 biology reports.

[20]  J. Rowley,et al.  Leukaemogenesis: more than mutant genes , 2010, Nature Reviews Cancer.

[21]  Howard Y. Chang,et al.  Genome-wide views of chromatin structure. , 2009, Annual review of biochemistry.

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

[23]  Mingming Jia,et al.  COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer , 2010, Nucleic Acids Res..

[24]  Adam A. Margolin,et al.  The Cancer Cell Line Encyclopedia enables predictive modeling of anticancer drug sensitivity , 2012, Nature.

[25]  Zhike Lu,et al.  Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification , 2011, Cell.

[26]  S. Ramaswamy,et al.  Systematic identification of genomic markers of drug sensitivity in cancer cells , 2012, Nature.

[27]  David M. Wilson,et al.  Fragment-based discovery of bromodomain inhibitors part 2: optimization of phenylisoxazole sulfonamides. , 2012, Journal of medicinal chemistry.

[28]  Dustin E. Schones,et al.  High-Resolution Profiling of Histone Methylations in the Human Genome , 2007, Cell.

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

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

[31]  P. L. Bergsagel,et al.  Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[32]  V. Verkhusha,et al.  Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2 , 2006, Nature.

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

[34]  Qiang Zhou,et al.  Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. , 2005, Molecular cell.

[35]  R. Tjian,et al.  Structure and function of a human TAFII250 double bromodomain module. , 2000, Science.

[36]  J. Brady,et al.  The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. , 2005, Molecular cell.

[37]  Karl Mechtler,et al.  Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins , 2001, Nature.

[38]  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.

[39]  M. Gallardo,et al.  RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination , 2007, Nature.

[40]  G. Garcia-Manero,et al.  Hypomethylating agents and other novel strategies in myelodysplastic syndromes. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  James M. Woolven,et al.  Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery. , 2012, Journal of medicinal chemistry.

[42]  R. King,et al.  Cell biology: Nondisjunction, aneuploidy and tetraploidy (Reply) , 2006, Nature.

[43]  Andrew J. Bannister,et al.  Regulation of chromatin by histone modifications , 2011, Cell Research.

[44]  Yi Zhang,et al.  Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. , 2011, Genes & development.

[45]  C. Allis,et al.  Covalent histone modifications — miswritten, misinterpreted and mis-erased in human cancers , 2010, Nature Reviews Cancer.

[46]  E. Segal,et al.  What controls nucleosome positions? , 2009, Trends in genetics : TIG.

[47]  M. Stratton,et al.  The cancer genome , 2009, Nature.

[48]  C. Allis,et al.  DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA , 2007, Nature.

[49]  Sean D. Taverna,et al.  How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers , 2007, Nature Structural &Molecular Biology.

[50]  S. Lowe,et al.  RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia , 2011, Nature.

[51]  Sohail Malik,et al.  The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation , 2010, Nature Reviews Genetics.

[52]  Scott A. Armstrong,et al.  MLL translocations, histone modifications and leukaemia stem-cell development , 2007, Nature Reviews Cancer.

[53]  R. Beddington,et al.  Growth and Early Postimplantation Defects in Mice Deficient for the Bromodomain-Containing Protein Brd4 , 2002, Molecular and Cellular Biology.

[54]  Andrew J. Bannister,et al.  Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain , 2001, Nature.

[55]  C. French.  Demystified molecular pathology of NUT midline carcinomas , 2008, Journal of Clinical Pathology.

[56]  Trevor J Pugh,et al.  Initial genome sequencing and analysis of multiple myeloma , 2011, Nature.

[57]  Tetsuya Nakamura,et al.  Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation , 2011, Nature Cell Biology.

[58]  P. Sandy,et al.  Targeting MYC dependence in cancer by inhibiting BET bromodomains , 2011, Proceedings of the National Academy of Sciences.

[59]  William B. Smith,et al.  Selective inhibition of BET bromodomains , 2010, Nature.

[60]  Yang Shi,et al.  Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression , 2007, Nature.