M Szyf

Summary

Affiliation: McGill University
Country: Canada

Publications

  1. ncbi request reprint Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health
    Michael J Meaney
    McGill Program for Study of Genes, Environment and Health, McGill University, Montreal, Canada
    Trends Mol Med 13:269-77. 2007
  2. doi request reprint The early-life social environment and DNA methylation
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Clin Genet 81:341-9. 2012
  3. pmc DNA methylation mediates persistent epileptiform activity in vitro and in vivo
    Ziv M Machnes
    Department of Pharmacology and Therapeutics McGill University, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e76299. 2013
  4. pmc Childhood chronic physical aggression associates with adult cytokine levels in plasma
    Nadine Provençal
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e69481. 2013
  5. pmc Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes
    Barbara Stefanska
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e68439. 2013
  6. pmc Methylated DNA binding domain protein 2 (MBD2) coordinately silences gene expression through activation of the microRNA hsa-mir-496 promoter in breast cancer cell line
    Sebastian Alvarado
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e74009. 2013
  7. pmc Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex
    Maral Tajerian
    Alan Edwards Centre for Research on Pain, Faculty of Medicine, McGill University, Montreal, Canada
    PLoS ONE 8:e55259. 2013
  8. pmc A method for purification, identification and validation of DNMT1 mRNA binding proteins
    Alexander Unterberger
    McGill University, 3655, Sir William Osler Promena, Montreal, QC, Canada
    Biol Proced Online 10:47-57. 2008
  9. ncbi request reprint Childhood abuse is associated with methylation of multiple loci in adult DNA
    Matthew Suderman
    Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal H3G 1Y6, QC, Canada
    BMC Med Genomics 7:13. 2014
  10. doi request reprint DNA methylation, behavior and early life adversity
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    J Genet Genomics 40:331-8. 2013

Collaborators

Detail Information

Publications112 found, 100 shown here

  1. ncbi request reprint Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health
    Michael J Meaney
    McGill Program for Study of Genes, Environment and Health, McGill University, Montreal, Canada
    Trends Mol Med 13:269-77. 2007
    ....
  2. doi request reprint The early-life social environment and DNA methylation
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Clin Genet 81:341-9. 2012
    ..Data that are consistent with this new role for DNA methylation as a mechanism for conferring an 'environment' specific identity to DNA will be discussed...
  3. pmc DNA methylation mediates persistent epileptiform activity in vitro and in vivo
    Ziv M Machnes
    Department of Pharmacology and Therapeutics McGill University, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e76299. 2013
    ....
  4. pmc Childhood chronic physical aggression associates with adult cytokine levels in plasma
    Nadine Provençal
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e69481. 2013
    ..This study investigates the association between chronic physical aggression during childhood and plasma cytokine levels in early adulthood...
  5. pmc Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes
    Barbara Stefanska
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e68439. 2013
    ..After further validation in a larger cohort, the identified DNA hypomethylated regions can become important candidate biomarkers for liver cancer diagnosis and prognosis, especially in populations with high risk for HCC development. ..
  6. pmc Methylated DNA binding domain protein 2 (MBD2) coordinately silences gene expression through activation of the microRNA hsa-mir-496 promoter in breast cancer cell line
    Sebastian Alvarado
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    PLoS ONE 8:e74009. 2013
    ..Taken together these results describe a novel cascade for gene regulation by DNA methylation whereby activation of a methylated microRNA by MBD2 that is associated with loss of methylation triggers repression of downstream targets. ..
  7. pmc Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex
    Maral Tajerian
    Alan Edwards Centre for Research on Pain, Faculty of Medicine, McGill University, Montreal, Canada
    PLoS ONE 8:e55259. 2013
    ..Changes in brain structure and cortical function that are associated with chronic pain conditions may therefore be mediated by epigenetic mechanisms...
  8. pmc A method for purification, identification and validation of DNMT1 mRNA binding proteins
    Alexander Unterberger
    McGill University, 3655, Sir William Osler Promena, Montreal, QC, Canada
    Biol Proced Online 10:47-57. 2008
    ..We then validated the role of this protein in the destabilization of DNMT1 mRNA. In this report, we detail the different approaches used for the isolation, the identification of a RNA binding protein and the validation of its role...
  9. ncbi request reprint Childhood abuse is associated with methylation of multiple loci in adult DNA
    Matthew Suderman
    Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal H3G 1Y6, QC, Canada
    BMC Med Genomics 7:13. 2014
    ..DNA methylation is a critical mechanism in epigenetic regulation. We aimed to establish whether childhood abuse was associated with adult DNA methylation profiles...
  10. doi request reprint DNA methylation, behavior and early life adversity
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    J Genet Genomics 40:331-8. 2013
    ..Particularly important is the environment early in life including both the prenatal and postnatal social environments. ..
  11. pmc Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex
    Sebastian Alvarado
    Department of Pharmacology and Therapeutics, McGill University, Faculty of Medicine, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Mol Pain 9:21. 2013
    ....
  12. doi request reprint DNA demethylation and cancer metastasis: therapeutic implications
    Moshe Szyf
    McGill University, Department of Pharmacology and Therapeutics, 3655 Sir William Osler Promenade, Montreal PQ, H3G 1Y6, Canada 1 514 398 7107 1 514 398 6690
    Expert Opin Drug Discov 3:519-31. 2008
    ..Conclusion: Both methylation and demethylation could be pharmacologically modulated. It is argued here that inhibition of hypomethylation might provide a new therapeutic approach to antimetastatic therapy...
  13. doi request reprint DNA methylation: a mechanism for embedding early life experiences in the genome
    Moshe Szyf
    McGill University
    Child Dev 84:49-57. 2013
    ..Examining the environmental circumstances associated with the onset and reversal of DNA methylation will be critical for understanding risk and resiliency...
  14. doi request reprint Mind-body interrelationship in DNA methylation
    Moshe Szyf
    Department of Pharmacology and Therapeutics, Sackler Program in Epigenetics and Psychobiology, McGill University, Montreal, Que, Canada
    Chem Immunol Allergy 98:85-99. 2012
    ..New data suggesting associations between DNA methylation patterns in white blood cells and the social environment will be discussed...
  15. pmc DNA methylation of SPARC and chronic low back pain
    Maral Tajerian
    Alan Edwards Centre for Research on Pain, McGill University, 740 Dr, Penfield Avenue, Montreal, Quebec, H3A 1A4, Canada
    Mol Pain 7:65. 2011
    ..We tested the hypothesis that DNA methylation down-regulates SPARC expression in chronic LBP in pre-clinical models and in patients with chronic LBP...
  16. ncbi request reprint Therapeutic implications of DNA methylation
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, PQ H3G 1Y6, Canada
    Future Oncol 1:125-35. 2005
    ..One of the main challenges however, is to understand the relative role of hypo- and hypermethylation in order to achieve a balance of epigenetic therapeutic agents with positive outcome and reduced adverse effects...
  17. ncbi request reprint DNA demethylation and cancer: therapeutic implications
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Que, Canada PQ H3G 1Y6
    Cancer Lett 211:133-43. 2004
    ..Understanding the relative roles of hypomethylation and hypermethylation in cancer has clear implications on the therapeutic use of agents targeting the DNA methylation machinery, which are discussed in this review...
  18. pmc DNA methylation, the early-life social environment and behavioral disorders
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada
    J Neurodev Disord 3:238-49. 2011
    ..This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed...
  19. pmc The implications of DNA methylation for toxicology: toward toxicomethylomics, the toxicology of DNA methylation
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Toxicol Sci 120:235-55. 2011
    ..The realization that long-range damage could be caused without changing the DNA sequence has important implications on the way we assess the safety of chemicals, drugs, and food and broadens the scope of definition of toxic agents...
  20. ncbi request reprint Targeting DNA methylation in cancer
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal PQ H3G 1Y6 Canada
    Bull Cancer 93:961-72. 2006
    ..It is now becoming clear however that hypomethylation also plays a role in cancer by activating genes required for invasion and metastasis. The potential therapeutic implications of targeting DNA methylation in cancer are discussed...
  21. ncbi request reprint DNA methylation and breast cancer
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osier Promenade, Montreal, Canada PQ H3G 1Y6
    Biochem Pharmacol 68:1187-97. 2004
    ..Future therapeutic application of either methylation or demethylation inhibitors in cancer therapy would require understanding of the relative role of these processes in the evolution of cancer...
  22. ncbi request reprint DNA methylation and demethylation as targets for anticancer therapy
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal PQ H3G 1Y6, Canada
    Biochemistry (Mosc) 70:533-49. 2005
    ..This review discusses the emerging role of demethylation in activation of pro-metastatic genes and the potential therapeutic implications of the demethylation machinery in metastasis...
  23. doi request reprint DNA methylation and demethylation probed by small molecules
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec, Canada H3G 1Y6
    Biochim Biophys Acta 1799:750-9. 2010
    ..This review will discuss DNA methylation and demethylation machineries, and their therapeutic potentials as targets for small molecule inhibitors...
  24. ncbi request reprint Maternal care, the epigenome and phenotypic differences in behavior
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    Reprod Toxicol 24:9-19. 2007
    ..We speculate that exposures to different environmental toxins, which affect the epigenetic machinery might alter long-established epigenetic programs in the brain...
  25. pmc The early life social environment and DNA methylation: DNA methylation mediating the long-term impact of social environments early in life
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University Montreal CA, USA
    Epigenetics 6:971-8. 2011
    ..However, several critical questions remain including the identification of mechanisms that transmit the signals from the social environment to the DNA methylation/demethylation enzymes...
  26. ncbi request reprint The dynamic epigenome and its implications in toxicology
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    Toxicol Sci 100:7-23. 2007
    ....
  27. doi request reprint Epigenetic therapeutics in autoimmune disease
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, QC, H3G 1Y6, Canada
    Clin Rev Allergy Immunol 39:62-77. 2010
    ..MBD2 was recently proposed to be involved in demethylation in T cells in lupus and is, therefore, a candidate target. Although this field is at its infancy, it carries great promise...
  28. ncbi request reprint The social environment and the epigenome
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, and Department of Psychiatry, Douglas Hospital Research Center, Montreal, Quebec, Canada
    Environ Mol Mutagen 49:46-60. 2008
    ..We speculate that exposures to different environmental toxins alters long-established epigenetic programs in the brain as well as other tissues leading to late-onset disease...
  29. pmc Epigenetics, behaviour, and health
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montréimeal, QC
    Allergy Asthma Clin Immunol 4:37-49. 2008
    ..In contrast to genetic sequence differences, epigenetic aberrations are potentially reversible, raising the hope for interventions that will be able to reverse deleterious epigenetic programming...
  30. doi request reprint The early life environment and the epigenome
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Biochim Biophys Acta 1790:878-85. 2009
    ....
  31. ncbi request reprint Epigenetic programming by maternal behavior
    Ian C G Weaver
    Douglas Hospital Research Center, 6875 LaSalle Blvd, Montreal, Quebec H4H 1R3, Canada
    Nat Neurosci 7:847-54. 2004
    ..Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible...
  32. ncbi request reprint DNA methyltransferase 1 knock down induces gene expression by a mechanism independent of DNA methylation and histone deacetylation
    Snezana Milutinovic
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 279:27915-27. 2004
    ..The implications of our data on the biological roles of DNMT1 and the therapeutic potential of DNMT1 inhibitors as anticancer agents are discussed...
  33. ncbi request reprint Ras induces a general DNA demethylation activity in mouse embryonal P19 cells
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    J Biol Chem 270:12690-6. 1995
    ..This demonstrates that the general DNA demethylation activity in mouse embryonal cells is controlled by an important cellular signal transducer and that DNA demethylase is a potential downstream effector of Ras...
  34. ncbi request reprint Epigenetic tête-à-tête: the bilateral relationship between chromatin modifications and DNA methylation
    Ana C D'Alessio
    Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6, Canada
    Biochem Cell Biol 84:463-76. 2006
    ..Cancer cells exhibit a paradoxical coexistence of global loss of DNA methylation with regional hypermethylation...
  35. ncbi request reprint How does DNA methyltransferase cause oncogenic transformation?
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, PQ, Canada
    Ann N Y Acad Sci 910:156-74; discussion 175-7. 2000
    ..Both DNMT1 and the demethylase play a causal role in cellular transformation and are candidate anticancer targets...
  36. ncbi request reprint DNA methyltransferase is a downstream effector of cellular transformation triggered by simian virus 40 large T antigen
    A Slack
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 274:10105-12. 1999
    ..These results suggest that elevation of DNA MeTase is an essential component of the oncogenic program induced by T antigen...
  37. ncbi request reprint Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life
    Ian C G Weaver
    Douglas Hospital Research Center, Montreal, Quebec H4H 1R3, Canada
    J Neurosci 25:11045-54. 2005
    ..These results demonstrate that, despite the inherent stability of the epigenomic marks established early in life through behavioral programming, they are potentially reversible in the adult brain...
  38. ncbi request reprint Downregulation of DNA (cytosine-5-)methyltransferase is a late event in NGF-induced PC12 cell differentiation
    J Deng
    Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal, PQ, Canada
    Brain Res Mol Brain Res 71:23-31. 1999
    ..We propose that NGF differentiation of PC12 cells represents a different paradigm of involvement of DNA methylation in terminal differentiation...
  39. ncbi request reprint Demethylase activity is directed by histone acetylation
    N Cervoni
    Department of Pharmacology and Therapeutics, McGill University, Montreal, PQ H3G 1Y6, Canada
    J Biol Chem 276:40778-87. 2001
    ..This provides a simple mechanism for explaining why active genes are not methylated...
  40. ncbi request reprint High intracellular concentrations of amyloid-beta block nuclear translocation of phosphorylated CREB
    D N Arvanitis
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    J Neurochem 103:216-28. 2007
    ....
  41. ncbi request reprint Quantum dot-induced epigenetic and genotoxic changes in human breast cancer cells
    Angela O Choi
    Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, McIntyre Medical Sciences Building, Montreal H3G 1Y6, Canada
    J Mol Med (Berl) 86:291-302. 2008
    ..These studies suggest that aside from genotoxic effects, nanoparticles could cause more subtle epigenetic changes which merit thorough examination of environmental nanoparticles and novel candidate nanomaterials for medical applications...
  42. ncbi request reprint Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites
    Ian C G Weaver
    McGill Program for the Study of Behavior, Genes and Environment, Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada
    Ann N Y Acad Sci 1024:182-212. 2004
    ..This paper summarizes the evidence in favor of these pathways as well as recent studies describing regulatory targets within the chromatin structure of the promoter region of the rat hippocampal glucocorticoid receptor gene...
  43. ncbi request reprint Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat
    Moshe Szyf
    McGill Program for the Study of Behavior, Genes and Environment, McGill University, Montreal, Canada
    Front Neuroendocrinol 26:139-62. 2005
    ..These findings demonstrate that an epigenomic state of a gene can be established through a behavioral mode of programming and that in spite of the inherent stability of this epigenomic mark, it is dynamic and potentially reversible...
  44. ncbi request reprint From maternal care to gene expression: DNA methylation and the maternal programming of stress responses
    Ian C G Weaver
    Douglas Hospital Research Centre, McGill University, Montreal, PQ, Canada
    Endocr Res 28:699. 2002
  45. ncbi request reprint A conserved 3'-untranslated element mediates growth regulation of DNA methyltransferase 1 and inhibits its transforming activity
    N Detich
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 276:24881-90. 2001
    ..These results support the hypothesis that deregulated expression of DNMT1 with the cell cycle is important for cellular transformation...
  46. ncbi request reprint Transgenic mice as a model of pre-clinical Alzheimer's disease
    M T Ferretti
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Curr Alzheimer Res 8:4-23. 2011
    ..Similar neuronal alterations might occur prior to clinical diagnosis in AD, during a yet undefined 'latent' stage. A better understanding of such pre-clinical AD might yield novel therapeutic targets and or diagnostic tools...
  47. ncbi request reprint Regulation of the DNA methylation machinery and its role in cellular transformation
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Prog Nucleic Acid Res Mol Biol 69:47-79. 2001
    ..Unraveling how the different components of the DNA methylation machinery interact to replicate the DNA methylation pattern, and how they are disrupted in cancer, is critical for understanding the molecular mechanisms of cancer...
  48. ncbi request reprint The DNA methylation machinery as a therapeutic target
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal, PQ, Canada H3G 1Y6
    Curr Drug Targets 1:101-18. 2000
    ....
  49. ncbi request reprint Targeting DNA methyltransferase in cancer
    M Szyf
    Department of Pharmacology, McGill University, Montreal, PQ, Canada
    Cancer Metastasis Rev 17:219-31. 1998
    ..This commentary discusses the possible mechanisms through which DNA methyltransferase participates in oncogenesis and the rationale for targeting it in cancer...
  50. ncbi request reprint Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines
    Jing Ni Ou
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Biochem Pharmacol 73:1297-307. 2007
    ..Taken together, our data provide evidence for a reversible crosstalk between histone acetylation and DNA demethylation, which has significant implications on the use of HDAC inhibitors as therapeutic agents...
  51. ncbi request reprint Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis
    Pouya Pakneshan
    Department of Medicine, McGill University, Montreal H3A 1A1, Canada
    J Biol Chem 279:31735-44. 2004
    ..Inhibition of hypomethylation can thus be used as a novel therapeutic approach to silence the pro-metastatic gene uPA and block breast cancer progression into the aggressive and metastatic stages of the disease...
  52. ncbi request reprint Maternal programming of defensive responses through sustained effects on gene expression
    Tie Yuan Zhang
    McGill Program for the Study of Behavior, Genes and Environment, McGill University, Canada
    Biol Psychol 73:72-89. 2006
    ....
  53. pmc The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes
    Ian C G Weaver
    Douglas Hospital Research Center, Montreal, Quebec, Canada H4H 1R3
    J Neurosci 27:1756-68. 2007
    ..The data are consistent with the hypothesis that NGFI-A participates in epigenetic programming of GR expression...
  54. ncbi request reprint The DNMT1 target recognition domain resides in the N terminus
    F D Araujo
    Departments of Pharmacology and Therapeutics, Biochemistry, and Experimental Medicine, McGill University, Montreal, PQ, H3G 1Y6, Canada
    J Biol Chem 276:6930-6. 2001
    ..Our results now indicate that the DNMT1-PCNA interaction can be disrupted by substrate binding to the DNMT1 N terminus. These results point toward new directions in our understanding of the structure-function of DNMT1...
  55. ncbi request reprint Towards a pharmacology of DNA methylation
    M Szyf
    Dept of Pharmacology and Therapeutics, McGill University, PQ, Montreal, Canada H3G 1Y6
    Trends Pharmacol Sci 22:350-4. 2001
    ..The regulatory activities of DNMT1 are proposed to be involved in cellular transformation and should, therefore, serve as the targets for novel anti-cancer agents...
  56. ncbi request reprint Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites
    I C Weaver
    McGill Program for the Study of Behavior, Genes and Environment, Douglas Hospital Research Centre, Department of Psychiatry, McGill University, 6875 LaSalle Blvd, Montreal, Quebec, Canada H4H 1R3
    Mol Cell Endocrinol 185:205-18. 2001
    ..This paper summarizes the evidence in favor of these pathways as well as recent studies describing regulatory targets on the promoter region of the rat hippocampal glucocorticoid receptor gene...
  57. ncbi request reprint Mechanisms of epigenetic silencing of the c21 gene in Y1 adrenocortical tumor cells
    M Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Endocr Res 26:921-30. 2000
    ..We present a model to explain the possible roles of the different components of the epigenome and the DNA methylation and demethylation machineries in silencing c21 gene expression...
  58. ncbi request reprint The role of DNA methyltransferase 1 in growth control
    M Szyf
    Department of Pharmacology and Therapeutics McGill University Montreal, Canada H3G 1Y6
    Front Biosci 6:D599-609. 2001
    ..The unique position of DNMT1 in the cell cycle is consistent with the hypothesis that it plays an important role in cancer...
  59. pmc Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome
    Michael J Meaney
    McGill Program for the Study of Behavior, Genes and Environment, Department of Pharmacology, McGill University, Douglas Hospital Research Centre, Montreal, Quebec, Canada
    Dialogues Clin Neurosci 7:103-23. 2005
    ....
  60. pmc Diet and the epigenetic (re)programming of phenotypic differences in behavior
    Patrick O McGowan
    Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
    Brain Res 1237:12-24. 2008
    ..Nutritional restriction during gestation could affect epigenetic programming in the brain. These findings provide evidence for a stable yet dynamic epigenome capable of regulating phenotypic plasticity through epigenetic programming...
  61. ncbi request reprint Targeting DNA methylation in cancer
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Que, Canada H3G 1Y6
    Ageing Res Rev 2:299-328. 2003
    ..This review discusses the possible role of DNA methyltranferases and demethylases in tumorigenesis and the possible pharmacological and therapeutic implications of the DNA methylation machinery...
  62. ncbi request reprint DNA methylation and cancer therapy
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Promenade, Quebec H3G 1Y6, Montreal, Canada
    Drug Resist Updat 6:341-53. 2003
    ....
  63. doi request reprint Epigenetics, DNA methylation, and chromatin modifying drugs
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Annu Rev Pharmacol Toxicol 49:243-63. 2009
    ..Understanding the epigenetic machinery and the differential roles of its components in specific disease states is essential for developing targeted epigenetic therapy...
  64. ncbi request reprint The methyl donor S-Adenosylmethionine inhibits active demethylation of DNA: a candidate novel mechanism for the pharmacological effects of S-Adenosylmethionine
    Nancy Detich
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1YG, Canada
    J Biol Chem 278:20812-20. 2003
    ..Taken together, our data support an alternative mechanism of action for AdoMet as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA...
  65. ncbi request reprint Utilization of antisense oligonucleotides to study the role of 5-cytosine DNA methyltransferase in cellular transformation and oncogenesis
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, PQ H3G 1Y6, Canada
    Methods 27:184-91. 2002
    ..Antisense oligonucleotides are applied to determine whether DNMT1 plays a causal role in specific cancer models ex vivo as well as in vivo...
  66. ncbi request reprint Alteration of the methylation status of tumor-promoting genes decreases prostate cancer cell invasiveness and tumorigenesis in vitro and in vivo
    Nicholas Shukeir
    Department of Medicine, McGill University, Montreal, Quebec, Canada
    Cancer Res 66:9202-10. 2006
    ....
  67. ncbi request reprint Maternal care as a model for experience-dependent chromatin plasticity?
    Michael J Meaney
    Douglas Hospital Research Center, 6875 LaSalle Boulevard, Montreal, Quebec H4H 1R3, Canada
    Trends Neurosci 28:456-63. 2005
    ..This review discusses the nature of this environmental programming--the mechanism by which it occurs in rats, its long-term implications, and opportunities for its reversal in rodents and ultimately in humans...
  68. ncbi request reprint A novel regulatory element in the dnmt1 gene that responds to co-activation by Rb and c-Jun
    A Slack
    Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal, Canada
    Gene 268:87-96. 2001
    ..The responsiveness of dnmt1 to this type of signal is consistent with an important role for regulated expression of dnmt1 during cellular differentiation...
  69. doi request reprint Epigenetic programming of phenotypic variations in reproductive strategies in the rat through maternal care
    N M Cameron
    Sackler Program for Epigenetics and Psychobiology at McGill University and Douglas University Mental Health Institute, McGill University, Montreal, Canada
    J Neuroendocrinol 20:795-801. 2008
    ..The tissue-specific nature of such effects may underlie the co-ordinated variation in multiple forms of reproductive function, resulting in distinct reproductive strategies...
  70. pmc Pharmacological inhibition of DNA methylation induces proinvasive and prometastatic genes in vitro and in vivo
    Bushra Ateeq
    Department of Medicine, McGill University, Montreal, Quebec, Canada
    Neoplasia 10:266-78. 2008
    ..These results draw attention to the critical role of demethylation as a potential mechanism that can promote the development and progression of tumor metastasis after demethylation therapy as an anticancer treatment...
  71. ncbi request reprint Epigenetic programming of stress responses through variations in maternal care
    Eric W Fish
    McGill Program for the Study of Behavior, Genes and Environment, Douglas Hospital Research Centre, McGill University, Montreal, Canada
    Ann N Y Acad Sci 1036:167-80. 2004
    ..Given the importance of early life and parent-child interactions to later behavior, prevention and intervention programs should target this critical phase of development...
  72. pmc Acetylation-induced transcription is required for active DNA demethylation in methylation-silenced genes
    Ana C D'Alessio
    Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada
    Mol Cell Biol 27:7462-74. 2007
    ..These data suggest that DNA demethylation follows rather than precedes early transcription and point towards a novel function for DNA demethylation as a memory of actively transcribed genes...
  73. ncbi request reprint Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes
    Snezana Milutinovic
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
    Carcinogenesis 28:560-71. 2007
    ..The implications of our results on the future therapeutic utilities of VPA in cancer will be discussed...
  74. ncbi request reprint Hypomethylation of urokinase (uPA) promoter in breast and prostate cancer: prognostic and therapeutic implications
    Pouya Pakneshan
    Department of Medicine, McGill University Health Center, Montreal, Canada
    Curr Cancer Drug Targets 5:471-88. 2005
    ..In this chapter, we will review DNA methylation as the underlying molecular mechanism regulating uPA gene expression and its potential diagnostic, prognostic and therapeutic implication...
  75. pmc Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood
    Ian C G Weaver
    Douglas Hospital Research Center, Montreal, QC, Canada
    Proc Natl Acad Sci U S A 103:3480-5. 2006
    ..These results suggest that early-life experience has a stable and broad effect on the hippocampal transcriptome and anxiety-mediated behavior, which is potentially reversible in adulthood...
  76. pmc Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain
    Patrick O McGowan
    Department of Psychiatry, Douglas Mental Health University Institute, Montreal, Quebec, Canada
    PLoS ONE 3:e2085. 2008
    ..rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription...
  77. ncbi request reprint Altered mitogen-activated protein kinase signaling, tau hyperphosphorylation and mild spatial learning dysfunction in transgenic rats expressing the beta-amyloid peptide intracellularly in hippocampal and cortical neurons
    V Echeverria
    Department of Pharmacology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6
    Neuroscience 129:583-92. 2004
    ....
  78. ncbi request reprint Multiple isoforms of DNA methyltransferase are encoded by the vertebrate cytosine DNA methyltransferase gene
    J Deng
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 273:22869-72. 1998
    ..The data presented here point toward a new mechanism for generating diversity of DNA MeTases and possibly diverse DNA methylation patterns...
  79. ncbi request reprint A mammalian protein with specific demethylase activity for mCpG DNA
    S K Bhattacharya
    Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
    Nature 397:579-83. 1999
    ..The discovery of this DNA demethylase should provide a basis for the molecular and developmental analysis of the role of DNA methylation and demethylation...
  80. pmc Organ and gestational age effects of maternal nutrient restriction on global methylation in fetal baboons
    A Unterberger
    Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    J Med Primatol 38:219-27. 2009
    ..We tested the hypotheses that global methylation in fetal baboon demonstrates organ specificity, gestational age specificity, and changes with maternal nutritional status...
  81. ncbi request reprint Epigenomic stress response. Knockdown of DNA methyltransferase 1 triggers an intra-S-phase arrest of DNA replication and induction of stress response genes
    Snezana Milutinovic
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 278:14985-95. 2003
    ..Based on these data, we suggest that this stress response mechanism evolved to guard against buildup of DNA methylation errors and to coordinate inheritance of genomic and epigenomic information...
  82. ncbi request reprint Valproate induces replication-independent active DNA demethylation
    Nancy Detich
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6 Canada
    J Biol Chem 278:27586-92. 2003
    ....
  83. ncbi request reprint Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion
    Yongjing Guo
    Departments of Medicine and Pharmacology, McGill University Health Center, Montreal, Quebec H3A 1A1, Canada
    J Biol Chem 277:41571-9. 2002
    ..Taken together, these results provide insight into the mechanism regulating the transcription of the uPA gene in the complex multistep process of breast cancer progression...
  84. doi request reprint Environmental epigenomics: understanding the effects of parental care on the epigenome
    Patrick O McGowan
    Department of Psychiatry, McGill University, Montreal, Quebec H3G1Y6, Canada
    Essays Biochem 48:275-87. 2010
    ..In the present chapter, we will discuss evidence that epigenetic processes early in life play a role in defining inter-individual trajectories of behaviour, with implications for mental health in adulthood...
  85. pmc AUF1 cell cycle variations define genomic DNA methylation by regulation of DNMT1 mRNA stability
    Jerome Torrisani
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    Mol Cell Biol 27:395-410. 2007
    ..In this study, we demonstrate a link between AUF1, the RNA degradation machinery, and maintenance of the epigenetic integrity of the cell...
  86. ncbi request reprint Methylation and inhibition of expression of uPA by the RAS oncogene: divergence of growth control and invasion in breast cancer cells
    Pouya Pakneshan
    Department of Medicine and Department of Pharmacology, McGill University Health Center, Montreal, Canada
    Carcinogenesis 26:557-64. 2005
    ..This has important implications for new therapeutic approaches to metastasizing cancer...
  87. ncbi request reprint Dynamic epigenetic states of ribosomal RNA promoters during the cell cycle
    Shelley E Brown
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, Quebec H3G 1Y6, Canada
    Cell Cycle 7:382-90. 2008
    ..This data is consistent with the idea that epigenetic states are dynamic in somatic cells and might participate in physiological cellular responses...
  88. ncbi request reprint On the mechanism of demethylation of 5-methylcytosine in DNA
    Stefan Hamm
    Department of Chemistry, McGill University, Montreal, QB, Canada
    Bioorg Med Chem Lett 18:1046-9. 2008
    ..A mechanism of the DNA demethylation reaction is proposed based on this observation...
  89. pmc Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
    Patrick O McGowan
    Douglas Mental Health University Institute, 6875 LaSalle Boulevard, Montreal, Quebec, H4H 1R3, Canada
    Nat Neurosci 12:342-8. 2009
    ..These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression...
  90. ncbi request reprint The mouse DNA methyltransferase 5'-region. A unique housekeeping gene promoter
    J Rouleau
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    J Biol Chem 267:7368-77. 1992
    ..We suggest that the DNA MeTase promoter represents a new class of housekeeping gene promoters that was designed to ensure high fidelity regulation of gene expression...
  91. doi request reprint The epigenetics of social adversity in early life: implications for mental health outcomes
    Patrick O McGowan
    Department of Psychiatry, McGill University, Montreal, Quebec, Canada
    Neurobiol Dis 39:66-72. 2010
    ..In this regard, we will examine evidence for the possibility that epigenetic mechanisms can contribute to later-onset neurological dysfunction and disease...
  92. ncbi request reprint Promoter-specific activation and demethylation by MBD2/demethylase
    Nancy Detich
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 277:35791-4. 2002
    ..1His vector. We propose that a single protein possessing both repressor and demethylase functions has evolved to coordinate a program that requires suppression of some methylated genes and activation of others...
  93. doi request reprint DNA demethylation induced by the methyl-CpG-binding domain protein MBD3
    Shelley E Brown
    McGill University, Department of Pharmacology and Therapeutics, Montreal, Quebec, Canada H3G 1Y6
    Gene 420:99-106. 2008
    ..These data demonstrate a causal relationship between MBD3 and DNA demethylation of genomic targets in cells...
  94. ncbi request reprint The oncoprotein Set/TAF-1beta, an inhibitor of histone acetyltransferase, inhibits active demethylation of DNA, integrating DNA methylation and transcriptional silencing
    Nadia Cervoni
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 277:25026-31. 2002
    ....
  95. ncbi request reprint Extracting DNA demethylase activity from mammalian cells
    Moshe Szyf
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
    Methods Mol Biol 200:163-76. 2002
  96. ncbi request reprint Proliferating cell nuclear antigen associates with histone deacetylase activity, integrating DNA replication and chromatin modification
    Snezana Milutinovic
    Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal, Quebec H3G 1Y6, Canada
    J Biol Chem 277:20974-8. 2002
    ..Our results strengthen the role of PCNA as a factor coordinating DNA replication and epigenetic inheritance...
  97. doi request reprint Regional-specific global cytosine methylation and DNA methyltransferase expression in the adult rat hippocampus
    Shelley E Brown
    Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Oslar Promenade, and Douglas Hospital Research Center, Montreal, Quebec H3G 1Y6, Canada
    Neurosci Lett 440:49-53. 2008
    ....
  98. ncbi request reprint Variations in DNA methylation patterns during the cell cycle of HeLa cells
    Shelley E Brown
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Epigenetics 2:54-65. 2007
    ..This is the first demonstration of a dynamic DNA methylation pattern within a single cell cycle of a mature somatic cell. These data are important for our understanding of the stability of DNA methylation patterns in somatic cells...
  99. ncbi request reprint Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring
    Frances A Champagne
    Douglas Hospital Research Center, Montreal, Quebec, Canada H4H 1R3
    Endocrinology 147:2909-15. 2006
    ....