Discover the new role of spatial chromosomal organization of frequently mutated cancer proteins

  A new Weststar Institute study reveals the function of the ARID1A protein, which is encoded by a gene that is one of the most common mutations in human cancers. According to a study published in "Science Advances", ARID1A is involved in the spatial composition of the genome. Without ARID1A, it has a wide-ranging effect on overall gene expression. This discovery provides important information for decoding the molecular changes associated with certain cancers, especially ovarian cancer.

  "My laboratory is studying the role of ARID1A as a SWI/SNF complex in regulating gene expression," said the deputy director, senior researcher, gene expression regulation project professor and Wistar Institute. Said Dr. Zhang Rugang, the director of the joint project of the center. "Searching for a new interacting protein in this complex has discovered a new protein that provides a new perspective on the function of ARID1A as a genome-wide regulator of spatial chromosomal composition."

  The three-dimensional structure of genomic DNA determines how DNA molecules are stacked in the microscopic space while allowing each gene to be transcribed and expressed at the correct time. Researchers discovered that ARID1A interacts with the components of the lectin II complex. Lectin II complex regulates gene expression by organizing chromosome structure.

  Zhang added: "This is a fine-tuning process. We found that ARID1A plays an important role."

  "The result identified the genome of thrombin II on specific DNA regulatory elements called enhancers. It shows. Positioning. Therefore, when the function of ARID1A is lost due to gene mutation, the distribution of lectin II changes and the expression of many genes also changes. Zhang and his colleagues also discovered that through interaction with lectin II, ARID1A regulates how different parts of the chromosome are organized in space. These regions are called chromosomal regions and help specific genes.

  "Our discovery adds an important component to the field of cancer chromatin regulation," said Wu Shuai, one of the first authors of the study and a doctoral researcher in Dr. Zhang's laboratory. Yes, "By changing the special structure of the chromosome, the loss of the ARID1A gene has a much broader impact on gene expression than originally thought."