International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


FUNCTIONAL STUDIES OF PROTEINS THAT BIND TO METHYLATED DNA

Adrian Bird
Wellcome Trust Centre for Cell Biology
Institute of Cell and Molecular Biology
University of Edinburgh
The King's Buildings
Mayfield Road
Edinburgh EH9 3JR

Co-Authors: Brian Hendrich, Jacky Guy, Egor Prokhortchouk, Anna Prokhortchouk, Helle Jørgensen
Institutions: Wellcome Trust Centre for Cell Biology, Inst for Cell Biology, University of Edinburgh

Methylation affects cytosines at the DNA sequence 5'CpG in mammalian DNA and causes local silencing of gene expression. Proteins that bind to methylated DNA are likely mediators of silencing. MeCP2 is a relatively abundant chromosomal protein whose localisation in the nucleus is dependent on CpG methylation. MeCP2 can recruit histone deacetylases and therefore links DNA methylation with changes in chromatin structure. Mutations in the MECP2 gene are the primary cause of Rett syndrome, a progressive neurological disorder that affects girls. We used conditional gene disruption in mice to approach the function of MeCP2. Homozygous Mecp2-null mice appear normal until several weeks after birth when neurological symptoms appear. Mecp2+/- heterozygotes also initially appear normal and can raise normal litters, but eventually develop neurological symptoms that recall Rett Syndrome, including gait ataxia and breathing arrhythmia. MBDs 1 - 4 constitute a family of proteins containing a motif related to the methyl-CpG binding domain of MeCP2. One of these proteins, MBD2, also acts as a deacetylase-dependent transcriptional repressor in vivo. In the absence of MBD2, a component of the "MeCP1" complex in mouse cells is lost and repression of methylated genes is compromised in vivo. We recently identified yet another complex containing a novel methyl-CpG binding protein. This protein, Kaiso, binds tightly to a specific methylated sequence, but is unrelated to the MBD protein family. In order to address the functional significance of these proteins, we are disrupting the genes in mice and analysing the phenotypic consequences.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012