Sci Adv : The Corey team revealed that the recognition protein for the H3.3 mutation revealed the mechanism that promotes tumor development.

!---- histone H3 is one of the main components of the nuclear element, the basic unit of genetic material, its tail contains a variety of histone sorcin sorortization, and participates in the regulation of a variety of biological processes.in recent years, several research teams have discovered the presence of hemoglobin H3 on high frequency "Driver mutations" in tumor tissue, including K27M and G34R/V mutations in high-level childhood brain tumors, K36M mutations in cartilage cell tumors, and G34W/L mutations in bone cell tumors.recently, Associate Research Fellow Guo Rui of Fudan University's Institute of Biomedical Research and Professor Shi Yang of Harvard University, And Suzanne J. Professor Baker, in collaboration with Science Advances, published an article entitled "RACK7 recognizes H3.34R mutation to put of MHC class II complex components and their sle se in opoblastoma" and found and demonstrated that chromatin-recognized protein RACK7 can identify histones H3.3G34R mutations and inhibit major tissue-specific antigen complexes A possible molecular biological mechanism for histone H3.3G34R mutation to promote tumor occurrence is described.H3.3G34R mutation mainly occurs in children's glioblastoma (Glioblastoma multiformeme, GBM) patient tissue, who is responsible for the brain tumor according to the degree of malignancy of the tumor into four levels, GBM is the most malignant IV brain tumor, it is one of the most common solid brain tumors, five-year survival rate of less than 5%. Thethe study of the mechanism of the role of H3.3G34R mutation in brain tumors is of great significance to the treatment of GBM.the team found that RACK7 can identify polypeptides and recombinant nucleosomes containing H3.3G34R mutations in vitro specifically through in vitro purification of recombinant proteins.and prove that the PHD domain of RACK7 is the key domain to identify H3.3G34R mutations.RACK7 isolated purified cultures from pediatric glioblastoma segregated in vitro specific identification of H3.3G34R mutations to obtain glioblastoma cell lines containing H3.3G34R mutations.rack7 can bind chromatin in two H3.3G34R cell lines, and after the H3.3G34R mutation was corrected to wild H3.3 by CRISPR/Cas9, the specific recognition of chromatin in RACK7 was significantly reduced.to further verify the relationship between RACK7 and H3.3G34R, the team found that correcting H3.3G34R to H3.3 wild type or knocking out RACK7 caused changes in the expression of the same gene, including the MHC II molecule, its partner protein CD74, CIITA, and the follicle-related genes. further analysisfound that it was due to the key regulatory genes , CIITA and cystic gene chromatin, which identified the MHC II molecule in RACK7 in H3.3G34R cells.MHC II molecule is one of the main participants in T-cell-regulating cellular immunity process, which is expressed in antigen-derived cells, small glial cells, neural stem cells and other cells.the newly generated MHC II molecules are assembled on the nesiphone network, transferred through a variety of vesicle structures, in turn, processed until inserted into the cell membrane, are identified by CD4 plus T lymphocytes, and participate in the immune response.the study showed that the interaction between RACK7 and the H3.3G34R mutation affects the synthesis of MHC II molecules and the process of intracellular transport.in addition to inhibiting the MHC II immune response process, the team also found that RACK7 inhibits the expression of cell differentiation-related genes in tumor cells containing H3.3G34R mutations by interacting with the histone H3.3G34R mutation.at the same time, knocking out RACK7 or correcting the H3.3G34R mutation to wild type can reduce tumor cell metastasis and aggressiveness.suggests that the recruitment of RACK7 by H3.3G34R can have an effect on the tumor properties of glioblastoma cells in children. RACK7 knockout and H3.3G34R mutation to H3.3 can inhibit cell metastasis and invasion, the study identified the identifying sub-RACK7 of histone-driven mutation H3.3G34R, and demonstrated this interaction in the H3.3G34R cell line that was isolated and purified in tumor tissue. the study for the first time, it is pointed out that RACK7 inhibits the immune response of the MHC Class II system in H3.3G34R cells, maintaining the tumor characteristics of H3.3G34R cells. RACK7 may be a therapeutic target for this type of glioblastoma containing the H3.3G34R mutation. it is understood that the first authors of the study are Dr. Jia Fangfang, Li Ze And Guo Rui. Guo Rui Associate Researcher and Author of The Newsletter. H3.3G34R children's glioblastoma cell line was completed by professor Dr. Chen He of St Jude Children's Research Hospital, Professor Chen He. .