IBCS Seminar - Professor Adrian Bird

The identity of differentiated cell types is remarkably stable. This lecture will explore two ways in which this is achieved via proteins that interpret genomic signals to stabilize and optimize gene expression programs. Evidence will be presented that the chromatin protein MeCP2 interprets the local DNA methylation density to modulate gene expression levels in the mature brain. Loss of MeCP2 by mutation compromises neuronal function, leading to the neurological disorder Rett syndrome. A second signal that affects gene activity globally is DNA base composition. We found that the stem cell protein SALL4, which stabilizes the embryonic stem cell state, depends for its function on binding to short AT-rich DNA sequence motifs whose frequency fluctuates dependent on base composition. Loss of this protein as cells differentiate may facilitate the differentiation process by allowing up-regulation of differentiation genes.

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