TL;DR: It is reported that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells.
Abstract: Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator–cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.
TL;DR: In this paper, the authors provide compositions and methods for identifying compounds that modulate Cohesin-Mediator function and apply them to treating a disorder involving altered CO-mediator function.
Abstract: In some aspects, the present invention provides compositions and methods relating at least in part to modulation of the Cohesin-Mediator interaction. The invention provides compositions and methods useful for modulating Cohesin-Mediator function. The invention further provides compositions and methods useful for identifying compounds that modulate Cohesin-Mediator function. In some aspects, the invention provides compositions and methods useful for treating a disorder involving altered Cohesin-Mediator function.
TL;DR: Evidence suggests that cohesin acts as a novel topological device that traps chromosomal DNA within a large tripartite ring formed by its core subunits.
Abstract: The cohesin complex is a major constituent of interphase and mitotic chromosomes. Apart from its role in mediating sister chromatid cohesion, it is also important for DNA double-strand-break repair and transcriptional control. The functions of cohesin are regulated by phosphorylation, acetylation, ATP hydrolysis, and site-specific proteolysis. Recent evidence suggests that cohesin acts as a novel topological device that traps chromosomal DNA within a large tripartite ring formed by its core subunits.
TL;DR: It is shown here that separin is a cysteine protease related to caspases that alone can cleave Sccl in vitro and depends on a conserved protein called separin for sister chromatid separation.
TL;DR: The crystal structure of a bacterial SMC "hinge" region along with EM studies and biochemical experiments on yeast Smc1 and Smc3 proteins show that SMC protamers fold up individually into rod-shaped molecules.