Kruppel-like factors and the methylome

This proposal addresses the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their unique ability to function as pioneer factors in reprograming and in their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status acts to engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This work will provide a new global understanding of the interactions between the epigenetic and transcriptional programs of cells.