DNA methylation supports intrinsic epigenetic memory in mammalian cells.

Yong Qing Feng, Romain Desprat, Haiqing Fu, Emmanuel N. Olivier, Mei Lin Chii, Amanda Lobell, Shilpa N. Gowda, Mirit I. Aladjem, Eric E. Bouhassira

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

We have investigated the role of DNA methylation in the initiation and maintenance of silenced chromatin in somatic mammalian cells. We found that a mutated transgene, in which all the CpG dinucleotides have been eliminated, underwent transcriptional silencing to the same extent as the unmodified transgene. These observations demonstrate that DNA methylation is not required for silencing. The silenced CpG-free transgene exhibited all the features of heterochromatin, including silencing of transcriptional activity, delayed DNA replication, lack of histone H3 and H4 acetylation, lack of H3-K4 methylation, and enrichment in tri-methyl-H3-K9. In contrast, when we tested for transgene reactivation using a Cre recombinase-mediated inversion assay, we observed a marked difference between a CpG-free and an unmodified transgene: the CpG-free transgene resumed transcription and did not exhibit markers of heterochromatin whereas the unmodified transgene remained silenced. These data indicate that methylation of CpG residues conferred epigenetic memory in this system. These results also suggest that replication delay, lack of histone H3 and H4 acetylation, H3-K4 methylation, and enrichment in tri-methyl-H3-K9 are not sufficient to confer epigenetic memory. We propose that DNA methylation within transgenes serves as an intrinsic epigenetic memory to permanently silence transgenes and prevent their reactivation.

Original languageEnglish (US)
JournalPLoS Genetics
Volume2
Issue number4
DOIs
StatePublished - Apr 2006

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methylation
DNA methylation
DNA Methylation
Transgenes
Epigenomics
epigenetics
transgenes
DNA
Histones
cells
reactivation
Methylation
Heterochromatin
acetylation
heterochromatin
Acetylation
histones
assay
DNA replication
DNA Replication

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

DNA methylation supports intrinsic epigenetic memory in mammalian cells. / Feng, Yong Qing; Desprat, Romain; Fu, Haiqing; Olivier, Emmanuel N.; Chii, Mei Lin; Lobell, Amanda; Gowda, Shilpa N.; Aladjem, Mirit I.; Bouhassira, Eric E.

In: PLoS Genetics, Vol. 2, No. 4, 04.2006.

Research output: Contribution to journalArticle

Feng, Yong Qing ; Desprat, Romain ; Fu, Haiqing ; Olivier, Emmanuel N. ; Chii, Mei Lin ; Lobell, Amanda ; Gowda, Shilpa N. ; Aladjem, Mirit I. ; Bouhassira, Eric E. / DNA methylation supports intrinsic epigenetic memory in mammalian cells. In: PLoS Genetics. 2006 ; Vol. 2, No. 4.
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