Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

Mammalian euchromatic gene silencing results from the combined repressive effects of histone and DNA methyltransferases. Little is known of the mechanism by which these enzymes cooperate to induce silencing. Here we show that mammalian HP1 family members mediate communication between histone and DNA methyltransferases. In vitro, methylation of histone 3 Lys 9 by G9a creates a binding platform for HP1α, β, and γ. DNMT1 interacts with HP1 resulting in increased DNA methylation on DNA and chromatin templates in vitro. The functional and physical interaction can be recapitulated in vivo. Binding of GAL4-HP1 to a reporter construct is sufficient to induce repression and DNA methylation in DNMT1 wild-type but not DNMT1-null cells. Additionally, silencing of the Survivin gene coincides with recruitment of G9a and HP1 in DNMT1 wild-type but not null cells. We conclude that direct interactions between HP1 and DNMT1 mediate silencing of euchromatic genes.

Bibliography

Smallwood, A., Estève, P.-O., Pradhan, S., & Carey, M. (2007). Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes & Development, 21(10), 1169–1178.

Authors 4
  1. Andrea Smallwood (first)
  2. Pierre-Olivier Estève (additional)
  3. Sriharsa Pradhan (additional)
  4. Michael Carey (additional)
References 62 Referenced 283
  1. 10.1101/gad.1102803
  2. 10.1016/S1535-6108(02)00234-9
  3. 10.1038/35065138
  4. 10.1128/MCB.22.7.2124-2135.2002
  5. 10.1016/j.molcel.2006.07.018
  6. 10.1158/0008-5472.CAN-06-0101
  7. 10.1126/science.1078572
  8. 10.1128/MCB.25.23.10338-10351.2005
  9. 10.1002/j.1460-2075.1992.tb05607.x / EMBO J. / A synergistic increase in potency of a multimerized VP16 transcriptional activation domain by Emami, (1992)
  10. 10.1128/MCB.01576-06
  11. 10.1074/jbc.M404842200
  12. 10.1073/pnas.0407729102
  13. 10.1074/jbc.M606203200
  14. 10.1101/gad.1463706
  15. 10.1038/ncb1353
  16. 10.1101/gad.1110503
  17. 10.1093/nar/gkg332
  18. 10.1146/annurev.biochem.74.010904.153721
  19. 10.1021/bi047634t
  20. 10.1101/gad.281503
  21. 10.1016/j.gde.2006.02.013
  22. 10.1007/s00018-005-5287-9
  23. 10.1074/jbc.M106643200
  24. 10.1007/s10577-005-1018-1
  25. 10.1128/MCB.19.1.855 / Mol. Cell. Biol. / Activation domain-specific and general transcription stimulation by native histone acetyltransferase complexes by Ikeda, (1999)
  26. 10.1111/j.1365-2443.2006.01029.x
  27. 10.1038/nature731
  28. 10.1093/emboj/20.18.5232
  29. 10.1158/0008-5472.CAN-05-1980
  30. 10.1016/j.ymeth.2003.08.001
  31. 10.1016/j.cell.2007.02.005
  32. 10.1038/35065132
  33. 10.1074/jbc.M603724200
  34. 10.1073/pnas.162371699
  35. 10.1385/1592596819
  36. 10.1242/jcs.02291
  37. 10.1038/nrm1355
  38. 10.1093/emboj/cdg306
  39. {'key': '2021111607535752000_21.10.1169.39', 'first-page': '6456', 'article-title': 'Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′-deoxycytidine', 'volume': '62', 'author': 'Nguyen,', 'year': '2002', 'journal-title': 'Cancer Res.'} / Cancer Res. / Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′-deoxycytidine by Nguyen, (2002)
  40. 10.1093/emboj/18.22.6385
  41. 10.1074/jbc.M409604200
  42. 10.1016/S1097-2765(03)00477-5
  43. 10.1021/bi034160+
  44. 10.1016/S1521-6616(03)00204-3
  45. 10.1038/35010000
  46. 10.1016/S1097-2765(03)00479-9
  47. 10.1016/j.molcel.2004.05.026
  48. 10.1093/emboj/21.5.1121
  49. 10.18388/abp.2006_3337 / Acta Biochim. Pol. / Mammalian DNA methyltransferases by Siedlecki, (2006)
  50. 10.1016/j.tig.2003.09.007
  51. 10.1093/emboj/cdf657
  52. 10.1101/gad.989402
  53. 10.1101/gad.1284005
  54. 10.1038/ng1143
  55. {'key': '2021111607535752000_21.10.1169.55', 'first-page': '631', 'article-title': 'The role of mammalian DNA methyltransferases in the regulation of gene expression', 'volume': '10', 'author': 'Turek-Plewa,', 'year': '2005', 'journal-title': 'Cell. Mol. Biol. Lett.'} / Cell. Mol. Biol. Lett. / The role of mammalian DNA methyltransferases in the regulation of gene expression by Turek-Plewa, (2005)
  56. 10.1016/j.molcel.2005.06.011
  57. 10.1073/pnas.092025499
  58. 10.1007/s00412-005-0024-6
  59. 10.1038/sj.onc.1209763
  60. 10.1074/jbc.M211753200
  61. 10.1006/mthe.2002.0551
  62. 10.1016/j.cell.2006.08.003
Dates
Type When
Created 18 years, 3 months ago (April 30, 2007, 8:51 p.m.)
Deposited 3 years, 9 months ago (Nov. 16, 2021, 12:06 p.m.)
Indexed 1 day, 13 hours ago (Aug. 21, 2025, 1:27 p.m.)
Issued 18 years, 3 months ago (April 30, 2007)
Published 18 years, 3 months ago (April 30, 2007)
Published Online 18 years, 3 months ago (April 30, 2007)
Published Print 18 years, 3 months ago (May 15, 2007)
Funders 0

None

@article{Smallwood_2007, title={Functional cooperation between HP1 and DNMT1 mediates gene silencing}, volume={21}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1536807}, DOI={10.1101/gad.1536807}, number={10}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Smallwood, Andrea and Estève, Pierre-Olivier and Pradhan, Sriharsa and Carey, Michael}, year={2007}, month=apr, pages={1169–1178} }