Unexpected lapse of epigenetic regulation in development


An international team led by researchers of the Department of Molecular Biology has found that cells in embryos regulate genes differently than their counterparts in adult life. The surprising findings were published in a research article in the journal Genome Research (impact factor 11.3).

One of the major mechanisms cells use to silence genes involves DNA methylation. DNA methylation is known to repress gene activity in a wide range of cells. The scientific team profiled DNA methylation in Xenopus embryos, a model system for vertebrate development, using Next-Generation Sequencing technology. High levels of DNA methylation were detected in embryos, but surprisingly, highly methylated genes were found to be actively expressed. Moreover, genes abundantly expressed in mammalian embryonic stem cells are also frequently methylated, suggesting that this is a more general, conserved phenomenon.

The team therefore tested the ability of methylated DNA to repress gene transcription in different stages of development. Remarkably, early embryos do not strongly repress methylated genes, whereas oocytes and late stage embryos can actively repress genes when methylated. These findings have implications for our view of normal development and the reprogramming of cells to pluripotency, as these events have been shown to involve remodeling of epigenetic phenomena such as DNA methylation.

Bogdanovic, O., S.W. Long, S. J. van Heeringen, A.B. Brinkman, J.L. Gómez-Skarmeta, H.G. Stunnenberg, P.L. Jones and G.J.C. Veenstra. 2011. Temporal uncoupling of the DNA methylome and transcriptional repression during embryogenesis. Genome Research, Advance online publication June 2, 2011 (doi: 10.1101/gr.114843.110).

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