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Home > Active Motif's Podcast > CpG Islands, DNA Methylation, and Disease (Adrian Bird)
Podcast: Active Motif's Podcast
Episode:

CpG Islands, DNA Methylation, and Disease (Adrian Bird)
Category: Science & Medicine
Duration: 00:47:10
Publish Date: 2020-06-18 03:00:25
Description:

In this episode of the Epigenetics Podcast, we caught up with Sir Adrian Bird, Buchanan Professor of Genetics at the University of Edinburgh to talk about his work on CpG islands, DNA methylation, and the role of DNA methylation in human diseases.

 

Adrian Bird has been a pioneer in studying the CpG dinucleotide sequence. The CpG dinucleotide is distributed genome-wide and has several properties expected of a genomic signaling module. The extent to which CpG signaling is involved in development, differentiation, and disease is only just beginning to emerge. Adrian Bird's work indicates that proteins that bind methylated CpGs recruit chromatin modifying enzymes to reinforce gene silencing, whereas proteins that bind unmethylated CpGs promote the formation of active chromatin. These results suggest that CpG acts as a global modulator of genome activity.

 

One of the best-studied methyl-CpG binding proteins is MeCP2, which is almost as abundant as histones in neurons. MeCP2-deficient children acquire serious neurological disorders, in particular the autism spectrum disorder Rett Syndrome. Due to its monogenic origin, Rett Syndrome has become one of the most experimentally accessible of such disorders and studies of MeCP2 offer a golden opportunity to understand its complex pathology at a molecular level. Adrian Bird created a mouse model of Rett Syndrome which has accelerated the understanding of this disorder, most notably by demonstrating that advanced Rett-like symptoms in mice can be “cured” by reintroducing a functional MeCP2 gene.

  

In this interview, podcast host Stefan Dillinger and Adrian discuss CpG islands, DNA methylation, and how the discovery of MeCP2 lead to the discovery of a possible treatment of Rett Syndrome.

 

References

  • S. Lindsay, A. P. Bird (1987) Use of restriction enzymes to detect potential gene sequences in mammalian DNA (Nature) DOI: 10.1038/327336a0 
  • R. R. Meehan, J. D. Lewis, … A. P. Bird (1989) Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs (Cell) DOI: 10.1016/0092-8674(89)90430-3 
  • R. R. Meehan, J. D. Lewis, A. P. Bird (1992) Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA (Nucleic Acids Research) DOI: 10.1093/nar/20.19.5085 
  • Eric U. Selker, Nikolaos A. Tountas, … Michael Freitag (2003) The methylated component of the Neurospora crassa genome (Nature) DOI: 10.1038/nature01564 
  • Robert J. Klose, Shireen A. Sarraf, … Adrian P. Bird (2005) DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG (Molecular Cell) DOI: 10.1016/j.molcel.2005.07.021 
  • Jacky Guy, Jian Gan, … Adrian Bird (2007) Reversal of neurological defects in a mouse model of Rett syndrome (Science (New York, N.Y.)) DOI: 10.1126/science.1138389 
  • Daniel H. Ebert, Harrison W. Gabel, … Michael E. Greenberg (2013) Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR (Nature) DOI: 10.1038/nature12348

 

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