FIGURE 4.

Schematic model illustrating the possible outcomes of LIS1-MeCP2 interaction in the context of wild-type or Lis1±. LIS1, shown as a rainbow colored beta-propeller protein, MeCP2, shown as purple balloons, transcriptional activators and inhibitors (green and red balloons, respectively on the bottom), interact in the nucleoplasm, or in close vicinity to the DNA. Transcriptional activation or repression will result in changes in neuronal gene expression as well as adult mouse behavior. (Top) In the wild-type context, LIS1 can either bind to MeCP2 in close vicinity to the DNA, and either recruit transcriptional activators, or assist in MeCP2 binding to chromatin. In addition, LIS1 may bind to MeCP2 in the nucleoplasm. These interactions will result in transcriptional activation. In other loci, LIS1 can bind to MeCP2 in close vicinity to the DNA in association with transcriptional repressors, alternatively LIS1 may aid in recruitment of transcriptional repressors to MeCP2. An additional option may be that LIS1 interacts directly with transcriptional repressors and enhances their activity. These interactions will result in transcription repression. (Bottom) In the context of Lis1±, we can observe reduced LIS1 levels. The effect of LIS1 reduction will be dependent upon the affinity of the different protein interactions. In case of transcription activation, we expect that less LIS1 will be found in association with MeCP2 and transcriptional activators thus resulting in decreased transcription activation. In case of transcription repression, less LIS1 may results in increased levels of MeCP2 in the nucleoplasm and less in association with chromatin.