According to this study, researchers showing a trillion of cells in our body share the same genetic information and are derived from a single, fertilized egg. When this initial cell multiplies during fetal development, its daughter cells become more and more specialized. This process, called cell differentiation. The study has been published in Nature Structural and Molecular Biology.
This process gives rise to all the various cell types, such as nerve, muscle, or blood cells, which are diverse in shape and function and make up tissues and organs. Some of these molecules are a complex of proteins called the Polycomb Repressive Complex 2 (PRC2) that is involved in "silencing" genes so that they are not "read" by the cellular machinery that decodes genetic information, effectively keeping the genetic information in the "off" state.
In two new studies, a team of researchers led by Eva Nogales, senior faculty scientist in the Molecular Biophysics and Integrated Bioimaging (MBIB) Division, has gained insight into the structure of PRC2 and the ways in which it is regulated to affect gene silencing.
The structural descriptions of human PRC2 with its natural partners in the cell lend important insight into the mechanism by which the PRC2 complex regulates gene expression. This information could provide new possibilities for the development of therapies for cancer. PRC2 is a gene regulator that is vital for normal development.
Genomic DNA is packaged into nucleosomes, which are formed by histone proteins that have DNA wrapped around them. Histone proteins have long polypeptide tails that can be modified by the addition and removal of small chemical groups. This work is complemented by a second study that presents snapshots of PRC2 binding to the histone proteins that it modifies as a signal for gene silencing.
"PRC2 can simultaneously engage two nucleosomes," said Poepsel, first author of this study. "Our cryo-EM images help us understand how the complex can recognize the presence of a histone modification in one nucleosome and place the same tag onto a neighboring nucleosome."
This cascade of activity enables PRC2 to spread this modification over the entire neighboring gene loci, thereby marking it for silencing. PRC2 is essential to gene regulation and expression in all multicellular organisms. The findings from both studies open tremendous possibilities for combatting cancer while simultaneously expanding our knowledge of gene regulation at a molecular level.
"Because PRC2 is deregulated in cancers, it makes a good target for potential therapeutics," said Nogales. The fundamental understanding of PRC2 arising from these studies will have broad implications in both plant and animal biology.
Author concludes that research used cryo-electron microscopy (cryo-EM) and made use of the unique resources of the Bay Area Cryo-EM Facility.