How does DNA methylation prevent gene expression?
DNA methylation is often recognized by proteins that contain a conserved methyl-CpG binding domain (MBD). MBDs can bind to 5-methylated cytosine residues because these project into the major groove of DNA where DNA-protein interactions can occur without disrupting the double helical structure. When an MBD-containing protein binds to m5Cs in the promoter region of a gene, inhibition of transcription can occur. EXERCISE: MeCP2 is a mammalian protein that binds to mCpG sequences in dsDNA and it represses transcription by recruiting histone deacetylases. It is also essential for embryologic development and, when defective, can result in a condition known as “Rett Syndrome” which is usually seen in girls. The solution structure of the domain from MeCP2 that binds o methylated DNA was described in 1999 by Wakefield et.al. and its atomic coordinatesin the Protein Data Bank are 1qk9. Look at its structure and answer the following questions: Note to Students in Spring 2004 Course: This is a “wo