WAPL encodes the cohesin release factor WAPL. Cohesin, a ring-shaped protein complex of several subunits, plays an essential role in maintaining sister chromatid cohesion for example during DNA replication and has also important functions in DNA repair, spatial 3D genome organization and transcriptional regulation. WAPL is required to unload cohesin from the DNA and thus to facilitate separation of sister chromatids during cell division.

While the relevance of WAPL in cell division has been well understood, its exact function in regulating gene expression has remained unsolved. In a study published in Nature Genetics researchers now investigated in mouse embryonic stem cells how WAPL depletion impacts on cohesin binding and genome organization and gained new insights into the mechanism through which cohesin is involved in regulating gene expression. The researchers found that lack of WAPL leads to a change in the formation of cell-specific cohesin binding sites. They also showed by 3D genome structure analysis that the disturbed cycle of cohesin loading and unloading disrupts promoter-enhancer interactions, thus decreasing gene expression.