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DNA Methylation Affects Nuclear Organization and Histone Modifications

By Trevor | May 16, 2007

In a paper recently published in the Journal of Cell Biology, Gilbert et. al. use mutant mouse embryonic stem cells lacking DNA methylation to show that DNA methylation affects nuclear organization and nucleosome structure, but not chromatin compaction.

DNA methylation has been implicated in chromatin condensation and nuclear organization, especially at sites of constitutive heterochromatin. How this is mediated has not been clear. In this study, using mutant mouse embryonic stem cells completely lacking in DNA methylation, we show that DNA methylation affects nuclear organization and nucleosome structure but not chromatin compaction. In the absence of DNA methylation, there is increased nuclear clustering of pericentric heterochromatin and extensive changes in primary chromatin structure. Global levels of histone H3 methylation and acetylation are altered, and there is a decrease in the mobility of linker histones. However, the compaction of both bulk chromatin and heterochromatin, as assayed by nuclease digestion and sucrose gradient sedimentation, is unaltered by the loss of DNA methylation. This study shows how the complete loss of a major epigenetic mark can have an impact on unexpected levels of chromatin structure and nuclear organization and provides evidence for a novel link between DNA methylation and linker histones in the regulation of chromatin structure.

References:

Gilbert N, Thomson I, Boyle S, Allan J, Ramsahoye B, Bickmore WA. 2007. DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction. Journal of Cell Biology 177(3):401-411.
doi:10.1083/jcb.200607133

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    • Topics: methylation |

    3 Responses to “DNA Methylation Affects Nuclear Organization and Histone Modifications”

    1. Cells Weekly #30 « Migrations Says:
      May 20th, 2007 at 9:00 am

      [...] DNA methylation affects nuclear organization and histone modifications [...]

    2. sanjay rawat Says:
      May 20th, 2007 at 11:16 pm

      i am very interested about this article, please send me a copy of this article by mail

    3. Izra Says:
      May 22nd, 2007 at 9:43 am

      hi Trevor, you’re from Dr.Skinner’s group, right?
      then maybe you’ll find interesting this paper on PNAS about synthetic estrogen exposure and evolution:

      Kidd KA et al. PNAS 104(21):8897-8901
      http://www.pnas.org/cgi/content/abstract/104/21/8897

      regards.