DALE L DORSETT

..Here we survey the roles of cohesin in gene regulation and DNA repair, and how these functions vary from yeast to man...

..These mechanisms are poorly understood, but involve both partial gene repression in concert with Polycomb group proteins, and facilitating long-range looping, both between enhancers and promoters, and between CTCF protein binding sites...

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..The mechanisms by which cohesion factors regulate gene expression remain to be elucidated, but current data suggest that they likely regulate transcription in multiple ways...

..Other recent studies argue that these roles involve regulation of gene transcription...

..Such effects of cohesin on gene expression could be responsible for many of the developmental deficits that occur in Cornelia de Lange syndrome, which is caused by mutations in the human homolog of Nipped-B...

..Effects on chromatid cohesion are apparent in RBS/SC syndrome, but data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits...

..These results support the idea that direct regulation of cohesin function underlies the diverse functions of Nipped-B and its orthologs...

..We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome...

..These mechanisms are likely involved in the etiology of Cornelia de Lange syndrome, in which mutation of one copy of the NIPBL gene encoding the human Nipped-B ortholog causes diverse structural and mental birth defects...

..We also found that Nipped-B, Pds5, and the Wapl protein that interacts with Pds5 all play unique roles in cohesin chromosome binding...

..New studies indicate that adherin activity is coordinated with DNA replication and chromosome segregation, and that its dosage is critical for gene expression and human development...

..Based on these results, we propose that Nipped-A, through the action of the SAGA and Tip60 complexes, facilitates assembly of the Notch activator complex and target gene transcription...

..Thus, these studies demonstrate at least one mechanism by which cohesin can control gene expression...

..Here we demonstrate that the dRtf1 component of the Paf1 complex functions in Notch signaling...

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..These studies will increase understanding of long-range gene activation and illuminate fundamental mechanisms underlying some human genetic diseases. ..

..This will help illuminate the basic mechanisms underlying gene expression defects that occur in some human diseases. ..

..These experiments will help define the roles of CHIP in potentiating enhancer activity, and increase understanding of how remote enhancers regulate transcription. ..

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