Genomic DNA can be entangled in histogene octomers (H2A, The basic unit of chromatin-nuclear small bodies formed on H2B, H3 and H4) catalyzed up to 3 methyl groups to specific lysine (K) residues in the tails of histones H3 and H4, which are essential for regulating the structure and gene expression of chromatin, and the imbalance of histone lysine methyl transferase is often directly related to a variety of cancers and other diseases.
NSD family protein is a specific histoprotein H3 lysine 36 methyl transferase, NSD2 plays a key role in the pathogenesis of multiple myeloma and acute lymphoblastic leukemia in children.
Abnormal expressions of NSD1 and NSD3 are also directly related to the occurrence of a variety of human cancers, such as acute myeloid leukemia, breast cancer, lung squamous cell carcinoma and head and neck cancer;
researchers are not clear about the molecular mechanisms behind it. In the
article, researchers used state-of-the-art cryogenic cryoelectrogenic technology to capture the detailed three-dimensional molecular structure of a complex formed by NSDs proteins and nucleosomes, and found that combining NSD2 and NSD3 with nucleosomes facilitates the unstructuring of DNA near the connecting region, freeing up space that can be inserted into the NSD protein catalytic domain between the octopolymers and the unfolding parts of the DNA.
DNA and hismoglobin-specific contact between NSD2 or NSD3 and the nucleosome may accurately locate the enzyme to the nucleosome, which may explain the methylation specificity of HSK36.
In addition, the researchers found that mutual contact between NSD proteins and nucleosomes can be altered by mutations associated with relapsed cancers NSD2 and NSD3, which promote the proliferation of cancer cells and the growth of allogeneic transplant tumors;
original source: Li, W., Tian, W., Yuan, G. et al. Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases. Nature (2020). doi:10.1038/s41586-020-03069-8。