DNA damage repair and transcription

Abstract

The unique properties of eukaryotic DNA modified via methylation of cytosine residues are believed to result from the action of a conserved family of proteins, the MBD family. The prototype member of this family, MeCP2, was isolated independently in two laboratories. One group isolated MeCP2 as a methylated DNA-binding protein, the second as a sequence-specific DNA-binding protein. Multiple lines of evidence suggest that MeCP2 functions in assembly of specialized chromatin architecture. While initial findings pointed to an enzymatic mechanism involving histone modification for transcriptional repression mediated by MeCP2, emerging studies clearly provide exceptions to this model. In a recent study, highly compacted, unique chromatin structures were generated by stoichiometric binding of MeCP2 to model chromatin fibers. These findings support the likelihood that MeCP2 can utilize two independent, but not mutually exclusive, mechanisms to repress transcription: enzymatic and structural mechanisms.