Cell Rep: new functions of proteins that play a key role in tumors and rare diseases

June 26, 2019 / BIOON / - in a paper published in cell reports, the chromosomal dynamics team of Spain's National Cancer Research Center (CNIO), led by ana losada, described the new function of adhesin in mouse embryonic stem cells, which can help to understand and solve the causes of these diseases Annexin is a kind of protein complex, which is very important for chromosome separation in cell division Recent evidence shows that it also plays an important role in the three-dimensional genome structure The genome folds like origami, regulating the basic cell processes including gene expression, DNA replication and DNA repair Mutations in mucin have been found in some types of cancer and in rare diseases called mucinosis Photo source: molecular genetics unit There are two variants of CNIO binding protein and pluripotent binding protein, including SA1 or SA2 Although the gene encoding SA2 shows a higher mutation rate in some types of cancer (such as bladder cancer, acute myeloid leukemia or Ewing sarcoma), the mutation rate of SA1 is much lower In 2018, a team led by losada and Marc Marti renom of the National Center for genomic analysis (cnag CRG) conducted a study that revealed the different roles of each variation in human epithelial cells Now, CNIO researchers have further identified the role of each variant in the specific genomic structure of embryonic stem cells, pluripotent cells that produce all cell types of adult organisms By studying mouse embryonic stem cells - similar to human embryonic stem cells - losada and her team at CNIO published their findings in cell reports, showing that annexin-sa1 helps to distinguish different regions (TADS) of genomic tissue Annexin-sa2 helps regulate the expression of genes that play a role in maintaining stem cell pluripotency - the ability of stem cells to produce the properties of all cell types that make up an adult organism "It's very important for us to confirm that what we observe in human cells also occurs in different types of cells, such as mouse embryonic stem cells," said losada, the study's co-author "In addition, this study provides evidence for the new role of adhesins in the structure of embryonic stem cells "For the first time, we have shown the contribution of adhesins to the three-dimensional tissue of Polycomb domains," she added "Under the spotlight of cancer research, Polycomb domains are three-dimensional genome structures that only exist in embryonic stem cells, as if they were extra folds in genomic origami missing in differentiated tissue cells These regions are characterized by the presence of Polycomb complexes and are essential to prevent the expression of genes encoding proteins with specific functions during embryonic development Therefore, Polycomb complex is involved in the suppressor gene, otherwise it will help to start cell differentiation Studies have shown that annexin-sa2 also exists in these regions, where it retains a protein in the Polycomb complex "When the level of annexin-sa2 in cells decreases, so does the level of Polycomb protein in the relevant chromosomal region," said ana cuadrado, lead author of the study Therefore, when the chromosome folds loose, the expression of tissue-specific genes is not properly silenced, and stem cells are no longer pluripotent and can not work normally In addition, Polycomb domains interact in distant chromosomal regions, even in different chromosomes, thus promoting gene inhibition In the process of preserving Polycomb protein, binding protein-sa2 promoted this interaction Further research is needed to understand the relationship between intercellular adhesion proteins and Polycomb complex in differentiated cells and their possible contribution to the occurrence of cancer cells "We believe that these studies will help us understand the role of mucin mutations in cancer development and mucin disease, such as Cornelia de Langer syndrome "Losada concluded Reference: specific contributions of cohesin-sa1 and cohesin-sa2 to TADS and Polycomb domains in electromagnetic stem cells, cell reports (2019) Doi: 10.1016/j.cellep.2019.05.078