The cohesin complex is crucial for chromosome segregation during mitosis and has 
recently also been implicated in transcriptional regulation and chromatin 
architecture. The NIPBL protein is required for the loading of cohesin onto 
chromatin, but how and where cohesin is loaded in vertebrate cells is unclear. 
Heterozygous mutations of NIPBL were found in 50% of the cases of Cornelia de 
Lange Syndrome (CdLS), a human developmental syndrome with a complex phenotype. 
However, no defects in the mitotic function of cohesin have been observed so far 
and the links between NIPBL mutations and the observed developmental defects are 
unclear. We show that NIPBL binds to chromatin in somatic cells with a different 
timing than cohesin. Further, we observe that high-affinity NIPBL binding sites 
localize to different regions than cohesin and almost exclusively to the 
promoters of active genes. NIPBL or cohesin knockdown reduce transcription of 
these genes differently, suggesting a cohesin-independent role of NIPBL for 
transcription. Motif analysis and comparison to published data show that NIPBL 
co-localizes with a specific set of other transcription factors. In cells 
derived from CdLS patients NIPBL binding levels are reduced and several of the 
NIPBL-bound genes have previously been observed to be mis-expressed in CdLS. In 
summary, our observations indicate that NIPBL mutations might cause 
developmental defects in different ways. First, defects of NIPBL might lead to 
cohesin-loading defects and thereby alter gene expression and second, NIPBL 
deficiency might affect genes directly via its role at the respective promoters.