New Functions of a Key Protein in Tumor Development Are Discovered
Cohesin is a protein involved in the development of certain tumours, as it plays a fundamental role in cell division and in the three-dimensional structure of the genome. Some mutations in this protein are also present in the origin of rare diseases known as cohesinopathies. Recently, researchers at the Spanish National Cancer Research Center (CNIO) have discovered new functions in mouse cells of two variants of cohesin, cohesin-SA1 and cohesin-SA2.
Until now the role of cohesin variants in tissue cells was known but in the new work, published Cell Reports, researchers have studied their contribution to the genomic architecture of embryonic stem cells, those that are capable of generating the different cell types that make up a living being. In the study it is observed that cohesina-SA1 has more relevance when it comes to keeping the different regions (TADs) in which the genome is ordered differentiated, while cohesina-SA2 regulates the expression of the genes that are within the TADs, in particular, those that allow the maintenance of the pluripotency of the stem cells: the capacity to give origin to all the cells of the future organism.
These results are of great relevance because they reveal that what was previously observed in human tissue cells also occurs in mouse embryonic stem cells, which are remarkably different. In addition, the study provides a new finding related to the particular DNA structure of embryonic stem cells, which has regions called Polycomb domains. As the levels of cohesina-SA2 in the cells are reduced, the presence of Polycomb is also reduced, altering the levels of gene expression. The stem cell functions incorrectly, triggering the disease.
The in-depth study of cohesin is presented as fundamental for understanding the role of this type of mutation in certain types of cancer (bladder, acute myeloid leukaemia or Ewing sarcoma) and in cohesinopathies. The next step will be to investigate further the role of these proteins in the process of cell differentiation of stem cells and in the development of tumours.
Access to the original article: Specific contributions of cohesin-SA1 and cohesin-SA2 to TADs and Polycomb domains in embryonic stem cells. Cell reports.