New Studies Reveal The 3D Structure of Human PRC2 Protein

New Studies Reveal The 3D Structure of Human PRC2 Protein and Help Elucidate Its Mechanism of Gene Expression Regulation
By: Creative Biogene
 
SHIRLEY, N.Y. - July 30, 2018 - PRLog -- All the cells in our body contain the same genetic information, coming from a single germ cell. The daughter cell of this initial cell become more specialized while proliferating during fetal development. This process, called cell differentiation, produces a variety of cell types, such as nerve cells, muscle cells, or blood cells, which have different forms and functions and form tissues and organs. What makes the same genetic blueprint lead to diversity? The answer is related to the way genes are turned on or off during development.

Researchers from the Lawrence Berkeley National Laboratory have been studying molecules that act at the genetic level to produce different cell types. Some of these molecules are a complex known as Polycomb Repressive Complex 2 (PRC2), in which PRC2 is involved in the 'silenced' gene, which makes them not 'read' by the cellular machinery that decodes genetic information, effectively keeping genetic information 'closed'.

In two new studies, a team of researchers led by Eva Nogales, senior scientist at the Department of Molecular Biophysics and Integrated Bioimaging (MBIB) at the Lawrence Berkeley National Laboratory, processing a deeper understanding of the structure of PRC2 and the way it is regulated to affect gene silencing. The relevant research results were published online in the Journal of Science and the Journal of Nature Structural & Molecular Biology.

The results of these two studies provide a structural framework for understanding the function of PRC2, which for the first time illustrates how this type of molecule binds to its substrate. The structural description of human PRC2 and its natural partners in cells provides important insights into the mechanism by which the PRC2 complex regulates gene expression. This information may provide new possibilities for the development of cancer therapy.

PRC2 is a gene regulator that is essential for normal development. Genomic DNA is packaged into nucleosomes, which are formed by wrapping DNA around histones. Histones have long polypeptide tails that can be modified by the addition and removal of smaller chemical groups. These modifications affect the interaction of nucleosomes with each other and with other protein complexes in the nucleus. The function of PRC2 in cells is to make specific chemical changes in a histone (ie, histone H3), which turns off or silences the genes in the genomic region that has been modified by PRC2.

The researchers stated that it has been three years in order to understand this high-resolution structure of all parts or subunits that make up functional PRC2 and to visualize how additional protein subunits called cofactors can help regulate its activity. It is very clear that when the two cofactors (ie, AEBP2 and JARID2) bind to PRC2, they mimic the peptide tail of histone H3, suggesting that cofactors and histone tails work together to regulate PRC2 function. This structural study shows that there is a great hope for the development of new drugs that counteract PRC2 dysfunction in cancer.

PRC2 is essential for gene regulation and expression in all multicellular organisms. The results from these two studies have opened up enormous possibilities for cancer treatment, and have also expanded our understanding of gene regulation at the molecular level. As PRC2 has a dysregulation in cancer, it has become an excellent target for the development of potential drugs. The basic understanding of PRC2 from these studies will have a wide range of effects in plant and animal biology.

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