Keeping it in the family: diverse histone recognition by conserved structural folds

Epigenetic regulation of gene transcription relies on an array of recurring structural domains that have evolved to recognize post-translational modifications on histones. The roles of bromodomains, PHD fingers, and the Royal family domains in the recognition of histone modifications to direct transcription have been well characterized. However, only through recent structural studies has it been realized that these basic folds are capable of interacting with increasingly more complex histone modification landscapes, illuminating how nature has concocted a way to accomplish more with less. Here we review the recent biochemical and structural studies of several conserved folds that recognize modified as well as unmodified histone sequences, and discuss their implications on gene expression.

[1]  P. Evans,et al.  The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase Gcn5p , 2000, The EMBO journal.

[2]  Jinrong Min,et al.  Structure and function of histone methylation binding proteins. , 2009, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[3]  Berthold Göttgens,et al.  Molecular basis of histone H3K36me3 recognition by the PWWP domain of Brpf1 , 2010, Nature Structural &Molecular Biology.

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

[5]  Qiang Zhao,et al.  Structure of Human Spindlin1 , 2007, Journal of Biological Chemistry.

[6]  M. Cosgrove,et al.  A Conserved Arginine-containing Motif Crucial for the Assembly and Enzymatic Activity of the Mixed Lineage Leukemia Protein-1 Core Complex* , 2008, Journal of Biological Chemistry.

[7]  W. Rottbauer,et al.  Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex. , 2008, Genes & development.

[8]  Y. Hayashizaki,et al.  Solution structure of the PWWP domain of the hepatoma‐derived growth factor family , 2005, Protein science : a publication of the Protein Society.

[9]  C. Allis,et al.  Methylation of lysine 4 on histone H3: intricacy of writing and reading a single epigenetic mark. , 2007, Molecular cell.

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

[11]  K. Borden,et al.  Solution structure of the PHD domain from the KAP‐1 corepressor: structural determinants for PHD, RING and LIM zinc‐binding domains , 2001, The EMBO journal.

[12]  Tai-Huang Huang,et al.  PWWP module of human hepatoma-derived growth factor forms a domain-swapped dimer with much higher affinity for heparin. , 2007, Journal of molecular biology.

[13]  Randy J. Read,et al.  Methylation-state-specific recognition of histones by the MBT repeat protein L3MBTL2 , 2009, Nucleic acids research.

[14]  V. Rybin,et al.  Structural and functional analyses of methyl‐lysine binding by the malignant brain tumour repeat protein Sex comb on midleg , 2007, EMBO reports.

[15]  B. Cairns,et al.  Autoregulation of the rsc4 tandem bromodomain by gcn5 acetylation. , 2007, Molecular cell.

[16]  Yusuke Nakamura,et al.  Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism , 2008, Nature.

[17]  John D Aitchison,et al.  Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs. , 2006, Molecular cell.

[18]  H. Dyson,et al.  Structure of the PHD zinc finger from human Williams-Beuren syndrome transcription factor. , 2000, Journal of molecular biology.

[19]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[20]  Wolfgang Fischle,et al.  Binary switches and modification cassettes in histone biology and beyond , 2003, Nature.

[21]  Georges Mer,et al.  Structural Basis for the Methylation State-Specific Recognition of Histone H4-K20 by 53BP1 and Crb2 in DNA Repair , 2006, Cell.

[22]  Ming-Ming Zhou,et al.  Structure and Hemimethylated CpG Binding of the SRA Domain from Human UHRF1* , 2008, Journal of Biological Chemistry.

[23]  Howard Y. Chang,et al.  ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation. , 2009, Molecular cell.

[24]  Roberto Sanchez,et al.  Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. , 2004, Molecular cell.

[25]  Irene Luque,et al.  Molecular Basis of Histone H3K4me3 Recognition by ING4* , 2008, Journal of Biological Chemistry.

[26]  H. Dyson,et al.  Solution structure and acetyl-lysine binding activity of the GCN5 bromodomain. , 2000, Journal of molecular biology.

[27]  S. Khorasanizadeh,et al.  Molecular implications of evolutionary differences in CHD double chromodomains. , 2007, Journal of molecular biology.

[28]  Brian O. Smith,et al.  The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer , 2000, The EMBO journal.

[29]  M. Geyer,et al.  Structures of the Dual Bromodomains of the P-TEFb-activating Protein Brd4 at Atomic Resolution* , 2009, The Journal of Biological Chemistry.

[30]  C. Allis,et al.  Mouse Polycomb Proteins Bind Differentially to Methylated Histone H3 and RNA and Are Enriched in Facultative Heterochromatin , 2006, Molecular and Cellular Biology.

[31]  Chao Xu,et al.  Solution structure of human Brg1 bromodomain and its specific binding to acetylated histone tails. , 2007, Biochemistry.

[32]  Xing Wang Deng,et al.  Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. , 2006, Molecular cell.

[33]  H. Leonhardt,et al.  The PHD domain of Np95 (mUHRF1) is involved in large-scale reorganization of pericentromeric heterochromatin. , 2008, Molecular biology of the cell.

[34]  Yi Zhang,et al.  Tudor, MBT and chromo domains gauge the degree of lysine methylation , 2006, EMBO reports.

[35]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[36]  E. Appella,et al.  Structural insight into p53 recognition by the 53BP1 tandem Tudor domain. , 2010, Journal of molecular biology.

[37]  Ming-Ming Zhou,et al.  Mechanism and Regulation of Acetylated Histone Binding by the Tandem PHD Finger of DPF3b , 2010, Nature.

[38]  M. Horikoshi,et al.  Novel structural and functional mode of a knot essential for RNA binding activity of the Esa1 presumed chromodomain. , 2008, Journal of molecular biology.

[39]  S. Jacobs,et al.  Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail , 2002, Science.

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

[41]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.

[42]  W. Wooster,et al.  Crystal structure of , 2005 .

[43]  J. Glover,et al.  Structure of the BRCT Repeat Domain of MDC1 and Its Specificity for the Free COOH-terminal End of the γ-H2AX Histone Tail* , 2005, Journal of Biological Chemistry.

[44]  D. Patel,et al.  Malignant brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets. , 2003, Structure.

[45]  F. Mackenzie,et al.  Structural Studies of a Four-MBT Repeat Protein MBTD1 , 2009, PloS one.

[46]  Ming-Ming Zhou,et al.  Structural insights into selective histone H3 recognition by the human Polybromo bromodomain 2 , 2010, Cell Research.

[47]  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.

[48]  Ming-Ming Zhou,et al.  Structure and function of protein modules in chromatin biology. , 2006, Results and problems in cell differentiation.

[49]  Chao Xu,et al.  Structural basis for the recognition of methylated histone H3K36 by the Eaf3 subunit of histone deacetylase complex Rpd3S. , 2008, Structure.

[50]  Yi Zhang,et al.  Recognition of Histone H3 Lysine-4 Methylation by the Double Tudor Domain of JMJD2A , 2006, Science.

[51]  Tom J. Petty,et al.  Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks , 2004, Nature.

[52]  A. Murzin,et al.  Crystal Structure of the Malignant Brain Tumor (MBT) Repeats in Sex Comb on Midleg-like 2 (SCML2)* , 2003, Journal of Biological Chemistry.

[53]  M. Sattler,et al.  Structure and ligand binding of the extended Tudor domain of D. melanogaster Tudor-SN. , 2009, Journal of molecular biology.

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

[55]  B. Turner,et al.  Cellular Memory and the Histone Code , 2002, Cell.

[56]  X. Pei,et al.  Structural Basis for the Recognition of Histone H4 by the Histone-Chaperone RbAp46 , 2008, Structure.

[57]  D. Zink,et al.  Chromodomains are protein–RNA interaction modules , 2000, Nature.

[58]  Jon R. Wilson,et al.  Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks. , 2009, Molecular cell.

[59]  A. Jeltsch,et al.  Chromatin Targeting of de Novo DNA Methyltransferases by the PWWP Domain* , 2004, Journal of Biological Chemistry.

[60]  G. Stier,et al.  SMN Tudor domain structure and its interaction with the Sm proteins , 2001, Nature Structural Biology.

[61]  M. Bedford,et al.  Arginine methylation at a glance , 2007, Journal of Cell Science.

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

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

[64]  T. Pawson,et al.  Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi , 2009, Proceedings of the National Academy of Sciences.

[65]  A. Murzin,et al.  Structure of the Chromo Barrel Domain from the MOF Acetyltransferase* , 2005, Journal of Biological Chemistry.

[66]  A. Bird,et al.  Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals , 2003, Nature Genetics.

[67]  R. Schwartz,et al.  SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development. , 2010, Molecular cell.

[68]  Abdellah Allali-Hassani,et al.  L3MBTL1 recognition of mono- and dimethylated histones , 2007, Nature Structural &Molecular Biology.

[69]  Wei Yang,et al.  The plant homeodomain finger of RAG2 recognizes histone H3 methylated at both lysine-4 and arginine-2 , 2007, Proceedings of the National Academy of Sciences.

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

[71]  Andrew J. Bannister,et al.  JAK2 phosphorylates histone H3Y41 and excludes HP1α from chromatin , 2009, Nature.

[72]  J. Qin,et al.  ICBP90, a Novel Methyl K9 H3 Binding Protein Linking Protein Ubiquitination with Heterochromatin Formation , 2007, Molecular and Cellular Biology.

[73]  T. Cierpicki,et al.  High resolution structure of the HDGF PWWP domain: A potential DNA binding domain , 2006, Protein science : a publication of the Protein Society.

[74]  Eric Verdin,et al.  Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain. , 2002, Molecular cell.

[75]  Ming-Ming Zhou,et al.  Structural basis of site-specific histone recognition by the bromodomains of human coactivators PCAF and CBP/p300. , 2008, Structure.

[76]  S. Richard,et al.  Tudor Domains Bind Symmetrical Dimethylated Arginines* , 2005, Journal of Biological Chemistry.

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

[78]  J. Yates,et al.  Regulation of Set9-mediated H4K20 methylation by a PWWP domain protein. , 2009, Molecular cell.

[79]  V. Rybin,et al.  Decoding of Methylated Histone H3 Tail by the Pygo-BCL9 Wnt Signaling Complex , 2008, Molecular cell.

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

[81]  G. Orphanides,et al.  Molecular basis for the recognition of phosphorylated and phosphoacetylated histone h3 by 14-3-3. , 2005, Molecular cell.

[82]  S. Berger The complex language of chromatin regulation during transcription , 2007, Nature.

[83]  M. Bycroft,et al.  The malignant brain tumor repeats of human SCML2 bind to peptides containing monomethylated lysine. , 2008, Journal of molecular biology.

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

[85]  Jean-François Couture,et al.  Molecular recognition of histone H3 by the WD40 protein WDR5 , 2006, Nature Structural &Molecular Biology.

[86]  Mahavir Singh,et al.  Structural Ramification for Acetyl‐Lysine Recognition by the Bromodomain of Human BRG1 Protein, a Central ATPase of the SWI/SNF Remodeling Complex , 2007, Chembiochem : a European journal of chemical biology.

[87]  Jerry L. Workman,et al.  Crosstalk among Histone Modifications , 2008, Cell.

[88]  Ernest D Laue,et al.  Structural basis of HP1/PXVXL motif peptide interactions and HP1 localisation to heterochromatin , 2004, The EMBO journal.

[89]  E. López-Hernández,et al.  Solution structure and NMR characterization of the binding to methylated histone tails of the plant homeodomain finger of the tumour suppressor ING4 , 2006, FEBS letters.

[90]  Raquel Matos,et al.  Molecular recognition of histone lysine methylation by the Polycomb group repressor dSfmbt , 2009, The EMBO journal.

[91]  Alexey G. Murzin,et al.  Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9 , 2002, Nature.

[92]  Alexey Bochkarev,et al.  Structural basis for molecular recognition and presentation of histone H3 By WDR5 , 2006, The EMBO journal.

[93]  M. Horikoshi,et al.  Structural polymorphism of chromodomains in Chd1. , 2007, Journal of molecular biology.

[94]  Xiaodong Cheng,et al.  The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds , 2002, Nature Structural Biology.

[95]  R. Mantovani,et al.  Np95 Is a Histone-Binding Protein Endowed with Ubiquitin Ligase Activity , 2004, Molecular and Cellular Biology.

[96]  Yusuke Nakamura,et al.  ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain , 2004, Oncogene.

[97]  T. Hung,et al.  Histone H3K4me3 binding is required for the DNA repair and apoptotic activities of ING1 tumor suppressor. , 2008, Journal of molecular biology.

[98]  M. Bycroft,et al.  Structural variation in PWWP domains. , 2003, Journal of molecular biology.

[99]  Ming-Ming Zhou,et al.  Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing , 2008, Nature Structural &Molecular Biology.

[100]  M. Myers,et al.  Crystal structure of the HP1-EMSY complex reveals an unusual mode of HP1 binding. , 2006, Structure.

[101]  S. Jacobsen,et al.  The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix , 2008, Nature.

[102]  J. Min,et al.  Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. , 2003, Genes & development.

[103]  S. Raguz,et al.  Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. , 2010, Molecular cell.

[104]  Roberto Sanchez,et al.  The role of human bromodomains in chromatin biology and gene transcription. , 2009, Current opinion in drug discovery & development.

[105]  Ming-Ming Zhou,et al.  Biochemical Profiling of Histone Binding Selectivity of the Yeast Bromodomain Family , 2010, PloS one.

[106]  D. Patel,et al.  Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF , 2006, Nature.

[107]  Danny Reinberg,et al.  Human but Not Yeast CHD1 Binds Directly and Selectively to Histone H3 Methylated at Lysine 4 via Its Tandem Chromodomains* , 2005, Journal of Biological Chemistry.

[108]  Michael Sattler,et al.  High-resolution X-ray and NMR structures of the SMN Tudor domain: conformational variation in the binding site for symmetrically dimethylated arginine residues. , 2003, Journal of molecular biology.

[109]  A. Shilatifard,et al.  WDR5, a complexed protein , 2009, Nature Structural &Molecular Biology.

[110]  M. Cosgrove,et al.  Structure of WDR5 Bound to Mixed Lineage Leukemia Protein-1 Peptide* , 2008, Journal of Biological Chemistry.

[111]  D. Gell,et al.  Engineering a protein scaffold from a PHD finger. , 2003, Structure.

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

[113]  Robin C. Allshire,et al.  Dimerisation of a chromo shadow domain and distinctions from the chromodomain as revealed by structural analysis , 2000, Current Biology.

[114]  R. Kingston,et al.  Structural basis of histone H4 recognition by p55. , 2008, Genes & development.

[115]  M. Thompson Polybromo-1: the chromatin targeting subunit of the PBAF complex. , 2009, Biochimie.

[116]  Hongbin Sun,et al.  Solution structure of BRD7 bromodomain and its interaction with acetylated peptides from histone H3 and H4. , 2007, Biochemical and biophysical research communications.

[117]  Dinshaw J. Patel,et al.  Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger , 2009, Nature.

[118]  Masami Horikoshi,et al.  Crystal Structure of the Human BRD2 Bromodomain , 2006, Journal of Biological Chemistry.

[119]  Jeroen Krijgsveld,et al.  Cooperative binding of two acetylation marks on a histone tail by a single bromodomain , 2009, Nature.

[120]  P. Peterson,et al.  The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation , 2009, Nucleic acids research.

[121]  Min Gyu Lee,et al.  Recognition of Histone H3K4 Trimethylation by the Plant Homeodomain of PHF2 Modulates Histone Demethylation* , 2010, The Journal of Biological Chemistry.

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

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

[124]  K. Mitsuya,et al.  The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA , 2007, Nature.

[125]  B. Simon,et al.  NMR structure of the first phd finger of autoimmune regulator protein (AIRE1): insights into apeced , 2005 .

[126]  Sheryl K Elkin,et al.  A PHD Finger Motif in the C Terminus of RAG2 Modulates Recombination Activity*[boxs] , 2005, Journal of Biological Chemistry.

[127]  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.

[128]  A. Murzin,et al.  Structure of the chromatin binding (chromo) domain from mouse modifier protein 1 , 1997, The EMBO journal.

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

[130]  M. Yaffe,et al.  MDC1 Directly Binds Phosphorylated Histone H2AX to Regulate Cellular Responses to DNA Double-Strand Breaks , 2008, Cell.

[131]  C. Arrowsmith,et al.  Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1 , 2008, Nature.

[132]  T. Pawson,et al.  Reading protein modifications with interaction domains , 2006, Nature Reviews Molecular Cell Biology.

[133]  S. Jacobsen,et al.  UHRF1 Plays a Role in Maintaining DNA Methylation in Mammalian Cells , 2007, Science.

[134]  Vincenzo Pirrotta,et al.  Polycomb silencing mechanisms and the management of genomic programmes , 2007, Nature Reviews Genetics.

[135]  R. Kingston,et al.  WDR5 Interacts with Mixed Lineage Leukemia (MLL) Protein via the Histone H3-binding Pocket* , 2008, Journal of Biological Chemistry.

[136]  Tony Pawson,et al.  Eukaryotic Protein Domains as Functional Units of Cellular Evolution , 2009, Science Signaling.

[137]  C. Kimmel,et al.  The multidomain protein Brpf1 binds histones and is required for Hox gene expression and segmental identity , 2008, Development.

[138]  Jianping Ding,et al.  Molecular Basis of the Interaction of Saccharomyces cerevisiae Eaf3 Chromo Domain with Methylated H3K36* , 2008, Journal of Biological Chemistry.

[139]  Helena Santos-Rosa,et al.  Distinct transcriptional outputs associated with mono- and dimethylated histone H3 arginine 2 , 2009, Nature Structural &Molecular Biology.

[140]  Sebastian Maurer-Stroh,et al.  The Tudor domain 'Royal Family': Tudor, plant Agenet, Chromo, PWWP and MBT domains. , 2003, Trends in biochemical sciences.

[141]  J. Côté,et al.  The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing. , 2007, Molecular cell.

[142]  R. Guérois,et al.  The Tudor tandem of 53BP1: a new structural motif involved in DNA and RG-rich peptide binding. , 2004, Structure.

[143]  Xiang-Jiao Yang,et al.  The crystal structure of the ING5 PHD finger in complex with an H3K4me3 histone peptide , 2008, Proteins.

[144]  S. Khorasanizadeh,et al.  Corecognition of DNA and a methylated histone tail by MSL3 chromodomain , 2010, Nature Structural &Molecular Biology.

[145]  Wolfgang Fischle,et al.  Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. , 2007, Molecular cell.

[146]  S. Khorasanizadeh,et al.  Recognition of trimethyllysine by a chromodomain is not driven by the hydrophobic effect , 2007, Proceedings of the National Academy of Sciences.

[147]  Ming-Ming Zhou,et al.  Structure and site-specific recognition of histone H3 by the PHD finger of human autoimmune regulator. , 2009, Structure.

[148]  Ming-Ming Zhou,et al.  PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. , 2007, Molecular cell.

[149]  Jianping Ding,et al.  Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3 , 2006, Nucleic acids research.

[150]  Georges Mer,et al.  Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor , 2008, Nature Structural &Molecular Biology.