Wapl controls higher-order chromatin structure in interphase chromosomes (gene expression)

Mammalian genomes contain several billion base pairs of DNA which are packaged in chromatin fibers. At selected gene loci, cohesin complexes have been proposed to arrange chromatin fibers into higher-order structures, but it is poorly understood how cohesin performs this task, how important this function is for determining the structure of chromosomes, and how this process is regulated to allow changes in gene expression. Here we show that the cohesin release factor Wapl controls chromatin structure and gene regulation at numerous loci throughout the mouse genome. Conditional deletion of the Wapl gene leads to stable accumulation of cohesin on chromatin, chromatin compaction, altered gene expression, cell cycle delay, chromosome segregation defects and embryonic lethality. In Wapl deficient chromosomes, cohesin accumulates in an axial domain, similar to how condensins form a “scaffold” in mitotic chromosomes. We propose that Wapl controls chromatin structure and gene regulation by determining the residence time with which cohesin binds to DNA. 4 biological replicates for each genotype (Wapl +/F; Wapl -/F) treated with/without 4-OHT =16 samples