PRBB-CRG Sessions Adrian Bird

04/04/202512:00MARIE CURIEPRBB-CRG SessionsAdrian BirdUniversity of Edinburgh, Wellcome Centre for Cell Biology"Proteins that interpret genomic signals to stabilize cell identity"Host: CRG PhD Community - Rabia Gul AydinAbstract: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 transcription programs. 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. Late provision of MeCP2 restores normal brain function in Mecp2-null mice, indicating that phenotypic defects are readily reversible. A second genomic signal that affects gene activity globally is DNA base composition. The protein SALL4 stabilizes the embryonic stem cell state and depends for its function on recruitment of a corepressor complex to short AT-rich DNA sequence motifs. Silencing of the SALL4 gene as cells differentiate enables the differentiation process by up-regulating gene products that are required for differentiation. In both these cases, the evidence suggests that transcriptional regulation depends on the frequency of short, relatively frequent DNA sequence motifs across genetic loci.