Post Doctoral Fellowships
Dirk Schubeler, Ph.D.
Fred Hutchinson Cancer Research Center
"Characterization of MeCP2, MBD1 and MBD2 Binding and Activity In Vivo Using Targeted Methylation"
Mentor: Mark Groudine, M.D., Ph.D.
2-Year Award: $100,000
Lay Final Report (2003):
Rett Syndrome results from mutations in the gene that encodes the protein MeCP2. MeCP2 is thought to play a role in inhibiting the transcription of DNA that is methylated. During the two years of this fellowship we have made significant progress in studying DNA methylation and the role of MeCP2 in methylation-mediated repression. We have shown that MeCP2 binds specifically to methylated DNA in the cell and that this binding coincides with the inhibition of transcription. While these experiments support the current model of how MeCP2 functions, they do not allow the identification of all genes that are bound by MeCP2 and that are potentially mis-regulated in patients with RETT syndrome.
Thus we have developed new approaches to study DNA methylation and protein binding on a genome-wide scale using micro-arrays. Such technology should allow a global but detailed view of the activity of MeCP2 in normal cells and cells from patients with RETT syndrome.
Dirk Schubeler, Ph.D.Fred Hutchinson Cancer Research Center
"Characterization of MeCP2, MBD1 and MBD2 Binding and Activity In Vivo Using Targeted Methylation"
Mentor: Mark Groudine, M.D., Ph.D.
2-Year Award: $100,000
Lay Final Report (2003):
Rett Syndrome results from mutations in the gene that encodes the protein MeCP2. MeCP2 is thought to play a role in inhibiting the transcription of DNA that is methylated. During the two years of this fellowship we have made significant progress in studying DNA methylation and the role of MeCP2 in methylation-mediated repression. We have shown that MeCP2 binds specifically to methylated DNA in the cell and that this binding coincides with the inhibition of transcription. While these experiments support the current model of how MeCP2 functions, they do not allow the identification of all genes that are bound by MeCP2 and that are potentially mis-regulated in patients with RETT syndrome.
Thus we have developed new approaches to study DNA methylation and protein binding on a genome-wide scale using micro-arrays. Such technology should allow a global but detailed view of the activity of MeCP2 in normal cells and cells from patients with RETT syndrome.