Histone modifications for human epigenome analysis

Histones function both positively and negatively in the regulation of gene expression, mainly governed by post-translational modifications on specific amino acid residues. Although histone modifications are not necessarily prerequisite codes, they may still serve as good epigenetic indicators of chromatin state associated with gene activation or repression. In particular, six emerging classes of histone H3 modifications are subjected for epigenome profiling by the International Human Epigenome Consortium. In general, transcription start sites of actively transcribed genes are marked by trimethylated H3K4 (H3K4me3) and acetylated H3K27 (H3K27ac), and active enhancers can be identified by enrichments of both monomethylated H3K4 (H3K4me1) and H3K27ac. Gene bodies of actively transcribed genes are associated with trimethylated H3K36 (H3K36me3). Gene repression can be mediated through two distinct mechanisms involving trimethylated H3K9 (H3K9me3) and trimethylated H3K27 (H3K27me3). Enrichments of these histone modifications on specific loci, or in genome wide, in given cells can be analyzed by chromatin immunoprecipitation (ChIP)-based methods using an antibody directed against the site-specific modification. When performing ChIP experiments, one should be careful about the specificity of antibody, as this affects the data interpretation. If cell samples with preserved histone–DNA contacts are available, evaluation of histone modifications, in addition to DNA methylaion, at specific gene loci would be useful for deciphering the epigenome state for human genetics studies.

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

[2]  Jian Cao,et al.  Epigenetic Regulation by Lysine Demethylase 5 (KDM5) Enzymes in Cancer , 2011, Cancers.

[3]  Yang Shi,et al.  Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity , 2012, Nature Structural &Molecular Biology.

[4]  Mazhar Adli,et al.  Whole-genome chromatin profiling from limited numbers of cells using nano-ChIP-seq , 2011, Nature Protocols.

[5]  K. Helin,et al.  Histone methyltransferases in cancer. , 2010, Seminars in cell & developmental biology.

[6]  G. Almouzni,et al.  HP1 and the dynamics of heterochromatin maintenance , 2004, Nature Reviews Molecular Cell Biology.

[7]  H. Kimura,et al.  The Organization of Histone H 3 Modifications as Revealed by a Panel of Specific Monoclonal Antibodies , 2008 .

[8]  Hyunmin Kim,et al.  Pre-mRNA splicing is a determinant of histone H3K36 methylation , 2011, Proceedings of the National Academy of Sciences.

[9]  B. Garcia,et al.  In Vivo Residue-specific Histone Methylation Dynamics* , 2009, The Journal of Biological Chemistry.

[10]  E. Wagner,et al.  Understanding the language of Lys36 methylation at histone H3 , 2012, Nature Reviews Molecular Cell Biology.

[11]  J. Ule,et al.  Explorer Psip 1 / Ledgf p 52 Binds Methylated Histone H 3 K 36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing , 2012 .

[12]  L. Mahadevan,et al.  Enhanced histone acetylation and transcription: a dynamic perspective. , 2006, Molecular cell.

[13]  R. Young,et al.  A Chromatin Landmark and Transcription Initiation at Most Promoters in Human Cells , 2007, Cell.

[14]  Bing Li,et al.  Readers of histone modifications , 2011, Cell Research.

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

[16]  Zachary D. Smith,et al.  DNA methylation: roles in mammalian development , 2013, Nature Reviews Genetics.

[17]  Kristian Helin,et al.  Histone demethylases in development and disease. , 2010, Trends in cell biology.

[18]  Chuan He,et al.  Mapping new nucleotide variants in the genome and transcriptome , 2012, Nature Biotechnology.

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

[20]  Jernej Ule,et al.  Psip1/Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing , 2012, PLoS genetics.

[21]  Benjamin A Garcia,et al.  Breaking the histone code with quantitative mass spectrometry , 2011, Expert review of proteomics.

[22]  M. Esteller,et al.  Cancer epigenetics reaches mainstream oncology , 2011, Nature Medicine.

[23]  P. Collas.  The Current State of Chromatin Immunoprecipitation , 2010, Molecular biotechnology.

[24]  Haruhiko Koseki,et al.  Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells , 2007, Nature Cell Biology.

[25]  Xiaobing Shi,et al.  Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation , 2012, Nature Structural &Molecular Biology.

[26]  Martin Renqiang Min,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[27]  Peter A. Jones,et al.  Cancer genetics and epigenetics: two sides of the same coin? , 2012, Cancer cell.

[28]  Hiroshi Kimura,et al.  Histone dynamics in living cells revealed by photobleaching. , 2005, DNA repair.

[29]  Gerben Duns,et al.  Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. , 2010, Cancer research.

[30]  Antoine H. F. M. Peters,et al.  H3K9/HP1 and Polycomb: two key epigenetic silencing pathways for gene regulation and embryo development. , 2013, Current topics in developmental biology.

[31]  Hiroshi Kimura,et al.  Tracking epigenetic histone modifications in single cells using Fab-based live endogenous modification labeling , 2011, Nucleic acids research.

[32]  H. Kimura,et al.  Human POGZ modulates dissociation of HP1α from mitotic chromosome arms through Aurora B activation , 2010, Nature Cell Biology.

[33]  P. Grant,et al.  Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation , 2011, The EMBO journal.

[34]  M. Esteller,et al.  Epigenetic modifications and human disease , 2010, Nature Biotechnology.

[35]  Karl Mechtler,et al.  Loss of the Suv39h Histone Methyltransferases Impairs Mammalian Heterochromatin and Genome Stability , 2001, Cell.

[36]  Sharon Y. R. Dent,et al.  Histone-modifying enzymes: regulators of developmental decisions and drivers of human disease. , 2012, Epigenomics.

[37]  Philippe Collas,et al.  Fast genomic μChIP-chip from 1,000 cells , 2009, Genome Biology.

[38]  M. Vidal,et al.  Role of histone H2A ubiquitination in Polycomb silencing , 2004, Nature.

[39]  Steven Henikoff,et al.  Histone modification: cause or cog? , 2011, Trends in genetics : TIG.

[40]  C. Woodcock,et al.  Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length , 2006, Chromosome Research.

[41]  Judith K. Brown,et al.  Polycomb group response elements in Drosophila and vertebrates. , 2013, Advances in genetics.

[42]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[43]  Laura S. Shankman,et al.  Detection of Histone Modifications at Specific Gene Loci in Single Cells in Histological Sections , 2012, Nature Methods.

[44]  Y. Shi,et al.  Tet family proteins and 5-hydroxymethylcytosine in development and disease , 2012, Development.

[45]  Michael Hampsey,et al.  Tails of Intrigue Phosphorylation of RNA Polymerase II Mediates Histone Methylation , 2003, Cell.

[46]  N. Brockdorff.  Noncoding RNA and Polycomb recruitment. , 2013, RNA.

[47]  Nathaniel D. Heintzman,et al.  Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome , 2007, Nature Genetics.

[48]  E. Wagner,et al.  Understanding the language of Lys 36 methylation at histone H 3 , 2014 .

[49]  A. Probst,et al.  Heterochromatin establishment in the context of genome-wide epigenetic reprogramming. , 2011, Trends in genetics : TIG.

[50]  S. Grewal,et al.  Heterochromatin revisited , 2007, Nature Reviews Genetics.

[51]  C. Ponting,et al.  Regulation of chromatin structure by site-specific histone H3 methyltransferases , 2000, Nature.

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

[53]  A. Probst,et al.  Heterochromatin maintenance and establishment: Lessons from the mouse pericentromere , 2011, Nucleus.

[54]  A. Schier,et al.  Bivalent histone modifications in early embryogenesis. , 2012, Current opinion in cell biology.

[55]  K. Helin,et al.  Polycomb group protein-mediated repression of transcription. , 2010, Trends in biochemical sciences.

[56]  Yang Shi,et al.  Reversal of Histone Lysine Trimethylation by the JMJD2 Family of Histone Demethylases , 2006, Cell.

[57]  James A. Cuff,et al.  A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells , 2006, Cell.

[58]  H. Kimura,et al.  The organization of histone H3 modifications as revealed by a panel of specific monoclonal antibodies. , 2008, Cell structure and function.

[59]  Gang Huang,et al.  Disordered epigenetic regulation in MLL-related leukemia , 2012, International Journal of Hematology.

[60]  Ole N Jensen,et al.  Proteomics in chromatin biology and epigenetics: Elucidation of post-translational modifications of histone proteins by mass spectrometry. , 2012, Journal of proteomics.

[61]  Huntington F Willard,et al.  Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[62]  Nathan C. Sheffield,et al.  The accessible chromatin landscape of the human genome , 2012, Nature.

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

[64]  B. Blencowe,et al.  Regulation of Alternative Splicing by Histone Modifications , 2010, Science.

[65]  Krishnamurthy Natarajan,et al.  Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes , 2012, Nature.

[66]  S. Spicuglia,et al.  H3K4 tri‐methylation provides an epigenetic signature of active enhancers , 2011, The EMBO journal.

[67]  Maria Carmo-Fonseca,et al.  Splicing enhances recruitment of methyltransferase HYPB/Setd2 and methylation of histone H3 Lys36 , 2011, Nature Structural &Molecular Biology.

[68]  S. Gygi,et al.  HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by nonoverlapping mechanisms. , 2008, Molecular cell.

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

[70]  Karolin Luger,et al.  New insights into nucleosome and chromatin structure: an ordered state or a disordered affair? , 2012, Nature Reviews Molecular Cell Biology.

[71]  D. Reinberg,et al.  The Polycomb complex PRC2 and its mark in life , 2011, Nature.

[72]  H. Kimura,et al.  Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET , 2010, Nature.

[73]  Paul Tempst,et al.  The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36 , 2006, Nature.

[74]  H. Kimura,et al.  Human inactive X chromosome is compacted through a PRC2-independent SMCHD1-HBiX1 pathway , 2013, Nature Structural &Molecular Biology.

[75]  B. Bernstein,et al.  Charting histone modifications and the functional organization of mammalian genomes , 2011, Nature Reviews Genetics.

[76]  W. Reik,et al.  Epigenetic Reprogramming in Plant and Animal Development , 2010, Science.

[77]  Jacques Côté,et al.  Perceiving the epigenetic landscape through histone readers , 2012, Nature Structural &Molecular Biology.

[78]  A. Shilatifard,et al.  A site to remember: H3K36 methylation a mark for histone deacetylation. , 2007, Mutation research.

[79]  R. Young,et al.  Histone H3K27ac separates active from poised enhancers and predicts developmental state , 2010, Proceedings of the National Academy of Sciences.

[80]  S. Bhaumik,et al.  Mixed lineage leukemia: histone H3 lysine 4 methyltransferases from yeast to human , 2010, The FEBS journal.

[81]  Christoph Bock,et al.  DNA methylation biomarkers in cancer: progress towards clinical implementation , 2012, Expert review of molecular diagnostics.

[82]  A. Shilatifard.  The COMPASS family of histone H3K4 methylases: mechanisms of regulation in development and disease pathogenesis. , 2012, Annual review of biochemistry.

[83]  Diana B. Marina,et al.  A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly , 2013, Nature.

[84]  Salvatore Spicuglia,et al.  Chromatin signatures of active enhancers , 2012, Nucleus.

[85]  J. Ragoussis,et al.  A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers , 2010, PLoS biology.

[86]  Yang Shi,et al.  Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. , 2010, Annual review of biochemistry.

[87]  David R. Liu,et al.  Conversion of 5-Methylcytosine to 5- Hydroxymethylcytosine in Mammalian DNA by the MLL Partner TET1 , 2009 .

[88]  Clifford A. Meyer,et al.  Model-based Analysis of ChIP-Seq (MACS) , 2008, Genome Biology.

[89]  M. G. Koerkamp,et al.  Balancing of histone H3K4 methylation states by the Kdm5c/SMCX histone demethylase modulates promoter and enhancer function. , 2013, Cell reports.

[90]  Peter J. Park,et al.  An assessment of histone-modification antibody quality , 2010, Nature Structural &Molecular Biology.

[91]  E. Greer,et al.  Histone methylation: a dynamic mark in health, disease and inheritance , 2012, Nature Reviews Genetics.