Cohesin regulates sister chromatid cohesion during the mitotic cell cycle with 
Nipped-B-Like (NIPBL) facilitating its loading and unloading. In addition to 
this canonical role, cohesin has also been demonstrated to play a critical role 
in regulation of gene expression in nondividing cells. Heterozygous mutations in 
the cohesin regulator NIPBL or cohesin structural components SMC1A and SMC3 
result in the multisystem developmental disorder Cornelia de Lange Syndrome 
(CdLS). Genome-wide assessment of transcription in 16 mutant cell lines from 
severely affected CdLS probands has identified a unique profile of dysregulated 
gene expression that was validated in an additional 101 samples and correlates 
with phenotypic severity. This profile could serve as a diagnostic and 
classification tool. Cohesin binding analysis demonstrates a preference for 
intergenic regions suggesting a cis-regulatory function mimicking that of a 
boundary/insulator interacting protein. However, the binding sites are enriched 
within the promoter regions of the dysregulated genes and are significantly 
decreased in CdLS proband, indicating an alternative role of cohesin as a 
transcription factor.