Genetic characterization of a family of mouse 5-methylcytosine binding protein genes

• Main Author: Tudor, Matthew, 1973-
• Other Authors: Rudolf Jaenisch.
• Format: Others
• Language: English
• Published: Massachusetts Institute of Technology 2006
• Subjects: Biology.
• Online Access: http://hdl.handle.net/1721.1/29993

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2003. === "September 2003." === Includes bibliographical references. === Cytosine-5-methylation has been associated with repression of transcription across eukaryotic phyla. In mammals, defects in methylation are associated with disease, developmental defects, and lethality. Furthermore, methylcytosine-specific binding proteins have been described which seem to effect the transcriptional repression associated with DNA methylation by modifying chromatin structure surrounding methylated sites. Whether these factors are, in fact, responsible for all of the essential functions of DNA methylation is unknown. We tested this possibility by creating mouse lines deficient for three factors shown to be methylcytosine-specific transcriptional repressors. Initial results suggest that these factors are not the only activities downstream of DNA methylation as their loss does not cause phenotypes as severe as loss of methylation. One of the factors studied, Mecp2 is the ortholog of the human gene mutated in Rett syndrome. Our deletion of Mecp2 in mice serves as a general model for the human disorder. Importantly, we find that transcription is not significantly deregulated in mice mutant for Mecp2, suggesting that the phenotypes seen are not a result of large-scale transcriptional derepression. === by Matthew Tudor. === Ph.D.