Enhancing transcription control – analysis of cohesin’s function in enhansosome-controlled transcription elongation.

Cohesin is a protein complex that plays a central role in controlling the high-order structure of chromosomes in eukaryotic cells and has recently been shown to have a motor activity that introduces loop structures into DNA in an ATP-dependent manner.

Cohesin´s function as a sister chromatid glue (mediator of sister chromatids cohesion) is a well-conserved function of Cohesin among eukaryotes.

The applicant has demonstrated that Cohesins bind to insulator sequences and enhancer regions of genes, and one of the roles of Cohesins is to regulate transcriptional elongation.

This role is closely related to known transcriptional elongation regulators such as the bromodomain protein BRD4 and the superelongation complex AFF4, and it is suggested to play an important role in the regulation of development and differentiation, and in the malignant transformation of cells.

Recently, it has been reported that an amorphous, dynamic, giant protein network controlled by "liquid-liquid phase separation" is formed on some enhancer DNAs, and it is also required to reconsider the enhancer complex (enhanceosome) as a collection of weak interactions.

The purpose of this application is to understand the transcriptional elongation control reaction by enhanceosomes on a molecular level, with a special focus on Cohesin, and to clarify its physiological significance. Genetic, genomic, and biochemical techniques will be used to achieve this goal.