Cohesin and condensin regulate chromosome topology and play an essential role in maintaining pluripotency in embryonic stem cells

Cohesin and condensin, two related protein complexes, play essential roles in ensuring the accurate segregation of the genome into daughter cells during cell division. However, the interaction between cohesin and condensin in embryonic stem cells remains unclear, as does the specific function of the meiosis-specific cohesin complex. Cohesin maintains the cohesion of replicated sister chromatids until their separation at anaphase, whereas condensin facilitates the reorganization of chromosomes into a highly compact structure characteristic of mitosis. First, we found via ChIP-seq analysis that cohesins (SMC3, RAD21, and REC8) and condensin (SMC4) share DNA binding sites in close proximity and directly interact with the insulator protein CTCF. Second, siRNA-regulated SMC3 depletion led to nuclear accumulation of SMC4. Third, embryonic stem (ES) cells uniquely harbor cohesin complexes containing the meiotic kleisin subunit REC8. RAD21 knockdown increased the proportion of SMC3-REC8 complexes. Our findings indicate that cohesin and condensin make important contributions to the functions of the chromosomal organization, and that meiotic cohesin may be specifically required for the mitotic program in ES cells.