The cohesin complex regulates sister chromatid pairing in early mitosis and, subsequently, in metaphase–anaphase transition, arranges for the sister chromatids to separate again. To do this, cohesin needs to access nucleosomal DNA and, in Nature, Ramin Shiekhattar and colleagues now report the identification of a DNA-binding site for cohesin. In addition, they propose a role for a chromatin-remodelling complex in mediating cohesin's access to chromatin.

Shiekhattar and co-workers isolated a chromatin-remodelling complex that contains SNF2h (a member of the ISWI family of chromatin remodelling proteins), subunits of the NuRD chromatin-remodelling complex and the cohesin complex. The authors found that an essential subunit of the cohesin complex, hRAD21, immunoprecipitates specifically with SNF2h and the NuRD component Mi2, and that recombinant hRAD21 binds to SNF2h directly.

Next, Shiekhattar and colleagues used chromatin immunoprecipitation to find in vivo binding sites for hRAD21 and SNF2h on chromosomes and identified a DNA site that contains Alu repeats — a class of short repeat sequences that are dispersed throughout the genome. However, not all of the seemingly indistinguishable Alu sites bound hRAD21, which indicates that the histones associated with the Alu-repeat DNA might be modified differently. Indeed, the authors found a correlation both between methylation of lysine 4 of histone H3 and the binding of SNF2h to chromatin, and between the acetylation of histone H3 or H4 and SNF2h binding.

In addition, the fact that Alu repeats are rich in CpG dinucleotides makes them potential targets for DNA methylation. In cells treated with a DNA methyltransferase inhibitor, binding of both SNF2h and hRAD21 was strong, which indicates, in addition to histone modification, a regulatory function for DNA methylation.

So, what is the functional significance of chromatin-remodelling activity in cohesin binding? To answer this question, Shiekhattar and colleagues created a SNF2h mutant defective in ATP hydrolysis, which is essential for activity. Cohesin binding was reduced in the presence of mutant SNF2h, indicating that chromatin-remodelling activity has an active role in loading cohesin onto chromatin.

These data reveal an interesting new function for the chromatin-remodelling machinery in DNA replication. The precise mechanism by which chromatin-remodelling complexes mediate the binding of cohesin to chromosomes will be the focus of future studies.