Epigenetic control

Epigenetics refers to mitotically and/or meiotically heritable variations in gene expression that are not caused by changes in DNA sequence. Epigenetic mechanisms regulate all biological processes from conception to death, including genome reprogramming during early embryogenesis and gametogenesis, cell differentiation and maintenance of a committed lineage. Key epigenetic players are DNA methylation and histone post‐translational modifications, which interplay with each other, with regulatory proteins and with non‐coding RNAs, to remodel chromatin into domains such as euchromatin, constitutive or facultative heterochromatin and to achieve nuclear compartmentalization. Besides epigenetic mechanisms such as imprinting, chromosome X inactivation or mitotic bookmarking which establish heritable states, other rapid and transient mechanisms, such as histone H3 phosphorylation, allow cells to respond and adapt to environmental stimuli. However, these epigenetic marks can also have long‐term effects, for example in learning and memory formation or in cancer. Erroneous epigenetic marks are responsible for a whole gamut of diseases including diseases evident at birth or infancy or diseases becoming symptomatic later in life. Moreover, although epigenetic marks are deposited early in development, adaptations occurring through life can lead to diseases and cancer. With epigenetic marks being reversible, research has started to focus on epigenetic therapy which has had encouraging success. As we witness an explosion of knowledge in the field of epigenetics, we are forced to revisit our dogma. For example, recent studies challenge the idea that DNA methylation is irreversible. Further, research on Rett syndrome has revealed an unforeseen role for methyl‐CpG‐binding protein 2 (MeCP2) in neurons. J. Cell. Physiol. 219: 243–250, 2009. © 2009 Wiley‐Liss, Inc.

[1]  M. Esteller Epigenetic changes in cancer , 2011, F1000 biology reports.

[2]  Albert Jeltsch,et al.  Cyclical DNA methylation of a transcriptionally active promoter , 2008, Nature.

[3]  Peter A. Jones,et al.  Epigenetics in cancer. , 2010, Carcinogenesis.

[4]  J. Davie,et al.  Increased genomic instability and altered chromosomal protein phosphorylation timing in HRAS‐transformed mouse fibroblasts , 2009, Genes, chromosomes & cancer.

[5]  M. Esteller,et al.  DNA methylomes, histone codes and miRNAs: tying it all together. , 2009, The international journal of biochemistry & cell biology.

[6]  George Reid,et al.  Marking time: the dynamic role of chromatin and covalent modification in transcription. , 2009, The international journal of biochemistry & cell biology.

[7]  Simon Kasif,et al.  Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains , 2008, PLoS genetics.

[8]  P. Hamet,et al.  Impact of genetic and epigenetic factors from early life to later disease. , 2008, Metabolism: clinical and experimental.

[9]  R. Roeder,et al.  30 nm chromatin fibre decompaction requires both H4-K16 acetylation and linker histone eviction. , 2008, Journal of molecular biology.

[10]  J. Davie,et al.  Mitotic partitioning of transcription factors , 2008, Journal of cellular biochemistry.

[11]  T. Mikkelsen,et al.  Genome-scale DNA methylation maps of pluripotent and differentiated cells , 2008, Nature.

[12]  T. Bestor,et al.  The Colorful History of Active DNA Demethylation , 2008, Cell.

[13]  G. Haegeman,et al.  Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF‐κB inhibition , 2008, The EMBO journal.

[14]  Paul Greengard,et al.  A phosphatase cascade by which rewarding stimuli control nucleosomal response , 2008, Nature.

[15]  A. Bird,et al.  DNA methylation landscapes: provocative insights from epigenomics , 2008, Nature Reviews Genetics.

[16]  Stephen T. C. Wong,et al.  MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription , 2008, Science.

[17]  Stephan C. Schuster,et al.  Nucleosome organization in the Drosophila genome , 2008, Nature.

[18]  J. Arthur,et al.  The forced swimming‐induced behavioural immobility response involves histone H3 phospho‐acetylation and c‐Fos induction in dentate gyrus granule neurons via activation of the N‐methyl‐d‐aspartate/extracellular signal‐regulated kinase/mitogen‐ and stress‐activated kinase signalling pathway , 2008, The European journal of neuroscience.

[19]  K. Helin,et al.  Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. , 2008, Genes & development.

[20]  Reiner Schulz,et al.  Regulation of alternative polyadenylation by genomic imprinting. , 2008, Genes & development.

[21]  K. Helin,et al.  Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2. , 2008, Genes & development.

[22]  S. Patra Ras regulation of DNA-methylation and cancer. , 2008, Experimental cell research.

[23]  M. Beato,et al.  Convergence on chromatin of non-genomic and genomic pathways of hormone signaling , 2008, The Journal of Steroid Biochemistry and Molecular Biology.

[24]  Yong-Yeon Cho,et al.  Mitogen- and stress-activated kinase 1-mediated histone H3 phosphorylation is crucial for cell transformation. , 2008, Cancer research.

[25]  K. Brami-Cherrier,et al.  Mitogen‐ and stress‐activated protein kinase‐1 deficiency is involved in expanded‐huntingtin‐induced transcriptional dysregulation and striatal death , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  Li Li,et al.  Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1 , 2008, Nucleic acids research.

[27]  Vladimir Benes,et al.  Transient cyclical methylation of promoter DNA , 2008, Nature.

[28]  D. Duboule,et al.  Epigenetic regulation of Hox gene activation: the waltz of methyls. , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[29]  Carolyn J. Brown,et al.  Epigenetics of cancer progression. , 2008, Pharmacogenomics.

[30]  T. Patel,et al.  Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes , 2008, Oncogene.

[31]  Jim Stalker,et al.  A Novel CpG Island Set Identifies Tissue-Specific Methylation at Developmental Gene Loci , 2008, PLoS biology.

[32]  Patrick O. McGowan,et al.  The social environment and the epigenome , 2008, Environmental and molecular mutagenesis.

[33]  J. Brotchie,et al.  Targeted delivery of an Mecp 2 transgene to forebrain neurons improves the behavior of female Mecp 2-deficient mice , 2008 .

[34]  K. Boon,et al.  In utero supplementation with methyl donors enhances allergic airway disease in mice. , 2008, The Journal of clinical investigation.

[35]  J. Arthur MSK activation and physiological roles. , 2008, Frontiers in bioscience : a journal and virtual library.

[36]  J. Sweatt,et al.  Covalent Modification of DNA Regulates Memory Formation , 2008, Neuron.

[37]  M. Bieda,et al.  Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes , 2007, Proceedings of the National Academy of Sciences.

[38]  Yi Zhang,et al.  New Nomenclature for Chromatin-Modifying Enzymes , 2007, Cell.

[39]  S. Shukla,et al.  Histone H3 phosphorylation at serine 10 and serine 28 is mediated by p38 MAPK in rat hepatocytes exposed to ethanol and acetaldehyde. , 2007, European journal of pharmacology.

[40]  J. Davie,et al.  Differential Distribution of Unmodified and Phosphorylated Histone Deacetylase 2 in Chromatin* , 2007, Journal of Biological Chemistry.

[41]  Huda Y. Zoghbi,et al.  The Story of Rett Syndrome: From Clinic to Neurobiology , 2007, Neuron.

[42]  Peter A. Jones,et al.  DNA methylation: The nuts and bolts of repression , 2007, Journal of cellular physiology.

[43]  M. Szyf,et al.  The dynamic epigenome and its implications in toxicology. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[44]  E. Ho,et al.  Dietary histone deacetylase inhibitors: from cells to mice to man. , 2007, Seminars in cancer biology.

[45]  R. Ghosh,et al.  MeCP2-Chromatin Interactions Include the Formation of Chromatosome-like Structures and Are Altered in Mutations Causing Rett Syndrome* , 2007, Journal of Biological Chemistry.

[46]  G. Almouzni,et al.  Marking histone H3 variants: how, when and why? , 2007, Trends in biochemical sciences.

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

[48]  D. Livingston,et al.  p21 transcription is regulated by differential localization of histone H2A.Z. , 2007, Genes & development.

[49]  M. Cosgrove Histone proteomics and the epigenetic regulation of nucleosome mobility , 2007, Expert review of proteomics.

[50]  J. Reul,et al.  Epigenetic mechanisms in stress-related memory formation , 2007, Psychoneuroendocrinology.

[51]  P. Zuzarte,et al.  Monoubiquitylation of H2A.Z Distinguishes Its Association with Euchromatin or Facultative Heterochromatin , 2007, Molecular and Cellular Biology.

[52]  Eric J. Nestler,et al.  Epigenetic regulation in psychiatric disorders , 2007, Nature Reviews Neuroscience.

[53]  C. Kunz,et al.  The enigmatic thymine DNA glycosylase. , 2007, DNA repair.

[54]  D. Riester,et al.  Histone deacetylase inhibitors—turning epigenic mechanisms of gene regulation into tools of therapeutic intervention in malignant and other diseases , 2007, Applied Microbiology and Biotechnology.

[55]  S. Henikoff,et al.  Histone Replacement Marks the Boundaries of cis-Regulatory Domains , 2007, Science.

[56]  K. Ozato,et al.  Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis. , 2007, Molecular human reproduction.

[57]  Zdenko Herceg,et al.  Epigenetics and cancer: towards an evaluation of the impact of environmental and dietary factors. , 2007, Mutagenesis.

[58]  David S. Lapointe,et al.  Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2 , 2007, Proceedings of the National Academy of Sciences.

[59]  A. Chess,et al.  Gene Body-Specific Methylation on the Active X Chromosome , 2007, Science.

[60]  A. Bird,et al.  Reversal of Neurological Defects in a Mouse Model of Rett Syndrome , 2007, Science.

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

[62]  E. Ho,et al.  Sulforaphane Retards the Growth of Human PC-3 Xenografts and Inhibits HDAC Activity in Human Subjects , 2007, Experimental biology and medicine.

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

[64]  O. McDonald,et al.  Concise Review: Epigenetic Mechanisms Contribute to Pluripotency and Cell Lineage Determination of Embryonic Stem Cells , 2007, Stem cells.

[65]  J. LaSalle The Odyssey of MeCP2 and parental imprinting. , 2007, Epigenetics.

[66]  S. Berger,et al.  In vivo dual cross-linking for identification of indirect DNA-associated proteins by chromatin immunoprecipitation. , 2006, BioTechniques.

[67]  R. Ghosh,et al.  Multiple Modes of Interaction between the Methylated DNA Binding Protein MeCP2 and Chromatin , 2006, Molecular and Cellular Biology.

[68]  M. Beato,et al.  Induction of progesterone target genes requires activation of Erk and Msk kinases and phosphorylation of histone H3. , 2006, Molecular cell.

[69]  Axel Imhof,et al.  PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state. , 2006, Molecular cell.

[70]  Eric C. Griffith,et al.  Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation , 2006, Neuron.

[71]  D. Reinberg,et al.  Histone H3 Lys 4 methylation: caught in a bind? , 2006, Genes & development.

[72]  W. Hung,et al.  Silencing of the metastasis suppressor RECK by RAS oncogene is mediated by DNA methyltransferase 3b-induced promoter methylation. , 2006, Cancer research.

[73]  J. Ausió,et al.  Histone variants--the structure behind the function. , 2006, Briefings in functional genomics & proteomics.

[74]  L. Gaudreau,et al.  Reuniting the contrasting functions of H2A.Z. , 2006, Biochemistry and cell biology = Biochimie et biologie cellulaire.

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

[76]  A. Bode,et al.  The role of histone H3 phosphorylation (Ser10 and Ser28) in cell growth and cell transformation , 2006, Molecular carcinogenesis.

[77]  J. Chelly,et al.  Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized , 2006, Nature Reviews Genetics.

[78]  Shihua He,et al.  Chromatin modification of the trefoil factor 1 gene in human breast cancer cells by the Ras/mitogen-activated protein kinase pathway. , 2006, Cancer research.

[79]  M. Pazin,et al.  Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions , 2006, Science.

[80]  C. Benz,et al.  Rapid alteration of microRNA levels by histone deacetylase inhibition. , 2006, Cancer research.

[81]  C. Jin,et al.  Distribution of histone H3.3 in hematopoietic cell lineages. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[82]  J. Miyazaki,et al.  Brd4 is required for recovery from antimicrotubule drug-induced mitotic arrest: preservation of acetylated chromatin. , 2005, Molecular biology of the cell.

[83]  H. Zoghbi,et al.  MeCP 2 dysfunction in Rett syndrome and related disorders , 2006 .

[84]  K. Robertson DNA methylation and human disease , 2005, Nature Reviews Genetics.

[85]  C. Wolberger,et al.  How does the histone code work? , 2005, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[86]  C. Der,et al.  Ras-mediated Loss of the Pro-apoptotic Response Protein Par-4 Is Mediated by DNA Hypermethylation through Raf-independent and Raf-dependent Signaling Cascades in Epithelial Cells* , 2005, Journal of Biological Chemistry.

[87]  E. Hurt,et al.  Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation. , 2005, Cancer research.

[88]  F. Iborra,et al.  MAP kinase-mediated phosphorylation of distinct pools of histone H3 at S10 or S28 via mitogen- and stress-activated kinase 1/2 , 2005, Journal of Cell Science.

[89]  J. Davie,et al.  Stimulation of the Ras-MAPK pathway leads to independent phosphorylation of histone H3 on serine 10 and 28 , 2005, Oncogene.

[90]  C. Monneret Histone deacetylase inhibitors. , 2005, European journal of medicinal chemistry.

[91]  C. Benz,et al.  Clinical development of histone deacetylase inhibitors as anticancer agents. , 2005, Annual review of pharmacology and toxicology.

[92]  Boyoung Lee,et al.  Light Stimulates MSK 1 Activation in the Suprachiasmatic Nucleus via a PACAP-ERK / MAP Kinase-Dependent Mechanism , 2005 .

[93]  Jef D Boeke,et al.  Regulated nucleosome mobility and the histone code , 2004, Nature Structural &Molecular Biology.

[94]  C. Peterson,et al.  Histones and histone modifications , 2004, Current Biology.

[95]  M. Caraglia,et al.  Acetylation of proteins as novel target for antitumor therapy: Review article , 2004, Amino Acids.

[96]  T. Curran,et al.  Transcription repression in oncogenic transformation: common targets of epigenetic repression in cells transformed by Fos, Ras or Dnmt1 , 2004, Oncogene.

[97]  G. Längst,et al.  Nucleosome remodeling: one mechanism, many phenomena? , 2004, Biochimica et biophysica acta.

[98]  Philip R. Gafken,et al.  Histone H3.3 is enriched in covalent modifications associated with active chromatin. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[99]  G. Almouzni,et al.  Histone H3.1 and H3.3 Complexes Mediate Nucleosome Assembly Pathways Dependent or Independent of DNA Synthesis , 2004, Cell.

[100]  J. LaSalle Paradoxical role of methyl-CpG-binding protein 2 in Rett syndrome. , 2004, Current topics in developmental biology.

[101]  D. Reinberg,et al.  The mediator coactivator complex: functional and physical roles in transcriptional regulation , 2003, Journal of Cell Science.

[102]  S. Henikoff,et al.  Epigenomic profiling using microarrays. , 2003, BioTechniques.

[103]  F. Aoki,et al.  Changes in histone acetylation during mouse oocyte meiosis , 2003, The Journal of cell biology.

[104]  Tom Misteli,et al.  The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[105]  J. Davie Inhibition of histone deacetylase activity by butyrate. , 2003, The Journal of nutrition.

[106]  Stuart Thomson,et al.  MSK2 and MSK1 mediate the mitogen‐ and stress‐induced phosphorylation of histone H3 and HMG‐14 , 2003, The EMBO journal.

[107]  G. Haegeman,et al.  Transcriptional activation of the NF‐κB p65 subunit by mitogen‐ and stress‐activated protein kinase‐1 (MSK1) , 2003, The EMBO journal.

[108]  A. V. van Kuilenburg,et al.  Histone deacetylases (HDACs): characterization of the classical HDAC family. , 2003, The Biochemical journal.

[109]  J. Martens,et al.  Cascade of Distinct Histone Modifications during Collagenase Gene Activation , 2003, Molecular and Cellular Biology.

[110]  S. Henikoff,et al.  The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. , 2002, Molecular cell.

[111]  K. Struhl,et al.  Dynamics of global histone acetylation and deacetylation in vivo: rapid restoration of normal histone acetylation status upon removal of activators and repressors. , 2002, Genes & development.

[112]  Erich A Nigg,et al.  Aurora‐B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation , 2002, Genes to cells : devoted to molecular & cellular mechanisms.

[113]  L. Mahadevan,et al.  Transcription: MAPK-regulated transcription: a continuously variable gene switch? , 2002, Nature Reviews Molecular Cell Biology.

[114]  J. Davie,et al.  Ser-10 phosphorylation of histone H3 and immediate early gene expression in oncogene-transformed mouse fibroblasts. , 2002, Cancer research.

[115]  M. Groudine,et al.  Methylation-Mediated Proviral Silencing Is Associated with MeCP2 Recruitment and Localized Histone H3 Deacetylation , 2001, Molecular and Cellular Biology.

[116]  L. Mahadevan,et al.  Independent dynamic regulation of histone phosphorylation and acetylation during immediate-early gene induction. , 2001, Molecular cell.

[117]  E. Verdin,et al.  Regulation of global acetylation in mitosis through loss of histone acetyltransferases and deacetylases from chromatin. , 2001, The Journal of biological chemistry.

[118]  A. Wolffe,et al.  Chromatin remodeling: why it is important in cancer , 2001, Oncogene.

[119]  A. Harel-Bellan,et al.  Histone acetylation and disease , 2001, Cellular and Molecular Life Sciences CMLS.

[120]  J. Ausió,et al.  Effects of Histone Acetylation on the Solubility and Folding of the Chromatin Fiber* , 2001, The Journal of Biological Chemistry.

[121]  M. J. Barratt,et al.  Phosphoacetylation of histone H3 on c‐fos‐ and c‐jun‐associated nucleosomes upon gene activation , 2000, The EMBO journal.

[122]  W. D. Cress,et al.  Histone deacetylases, transcriptional control, and cancer , 2000, Journal of cellular physiology.

[123]  C. Allis,et al.  Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation. , 2000, Molecular cell.

[124]  J. Davie,et al.  Control of chromatin remodeling. , 2000, Critical reviews in eukaryotic gene expression.

[125]  H. Zoghbi,et al.  Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 , 1999, Nature Genetics.

[126]  C. Allis,et al.  Increased Ser-10 Phosphorylation of Histone H3 in Mitogen-stimulated and Oncogene-transformed Mouse Fibroblasts* , 1999, The Journal of Biological Chemistry.

[127]  T. Curran,et al.  Role of DNA 5-methylcytosine transferase in cell transformation by fos. , 1999, Science.

[128]  Alan P. Wolffe,et al.  Disruption of Higher-Order Folding by Core Histone Acetylation Dramatically Enhances Transcription of Nucleosomal Arrays by RNA Polymerase III , 1998, Molecular and Cellular Biology.

[129]  J. Strouboulis,et al.  Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription , 1998, Nature Genetics.

[130]  Colin A. Johnson,et al.  Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex , 1998, Nature.

[131]  S. Hanash,et al.  Effect of mitogenic stimulation and DNA methylation on human T cell DNA methyltransferase expression and activity. , 1997, Journal of immunology.

[132]  C. Van Lint,et al.  Transcriptional activation and chromatin remodeling of the HIV‐1 promoter in response to histone acetylation. , 1996, The EMBO journal.

[133]  T. Schlake,et al.  Scaffold-attached regions (SAR elements) mediate transcriptional effects due to butyrate. , 1992, Biochemistry.

[134]  J. Davie,et al.  Histone acetylation alters the capacity of the H1 histones to condense transcriptionally active/competent chromatin. , 1990, The Journal of biological chemistry.

[135]  M. Solomon,et al.  Formaldehyde-mediated DNA-protein crosslinking: a probe for in vivo chromatin structures. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[136]  M. Perry,et al.  Histone acetylation increases the solubility of chromatin and occurs sequentially over most of the chromatin. A novel model for the biological role of histone acetylation. , 1982, The Journal of biological chemistry.