A complex network of biochemical pathways keeps the living organism healthy and alive. These are surprisingly resilient in adapting to environmental changes, but they do sometimes go wrong. Understanding these mechanisms is a central tenet in medicine to cure illness more efficiently.
The discovery by CSI Singapore researchers will likely improve the understanding of how normal stem cells function and could possibly lead to insights into disease. Image Credit: National University of Singapore.
A research team headed by Professor Daniel Tenen of the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has discovered a major molecular “switch” that regulates how cells switch their genes off and on. This method guarantees that the cell executes its assigned functions in the body adequately and correctly.
The researchers used hematopoietic stem cells as an example. These are essential cells that replenish the blood cells in the body during the entire lifespan.
The genes of a cell are encoded in long DNA sequences that coil up into extremely elaborate structures known as chromosomes. The shape of the chromosomes must be continuously tuned for the right genes to be expressed at the correct times and in the correct quantities in the cell.
This is accomplished by a protein known as CTCF, which binds to sections of the DNA that contain a certain sequence of codes and creates a loop in the DNA that stimulates the required gene.
However, the researchers discovered another protein named ZF143 that regulates CTCF activity level. This so-called “zinc finger protein” has a protruding molecular appendage that retains a zinc atom and confers the desired chemical properties on the protein.
ZNF143 was deactivated by the researchers using molecular markers to locate and delete its gene. They discovered that hematopoietic stem cells lacking ZNF143 were unable to generate new blood cells. In this situation, it may result in severe diseases such as anemia.
The study results were published on January 4th, 2021, in the journal Nature Communications.
Their development would almost certainly enhance the understanding of how normal stem cells function and can contribute to new insights into disease.
Findings from this study has advanced our understanding of the regulatory mechanisms of CTCF-DNA binding and gene expression. It will be of great interest to investigate whether these findings have relevance to developmental disorders and cancers.”
Daniel Tenen, Professor, Cancer Science Institute of Singapore, National University of Singapore
Moving ahead, the team intends to investigate the molecular structure of the proteins involved to get a better understanding of the mechanism and how it can be changed.
Zhou, Q., et al. (2021) ZNF143 mediates CTCF-bound promoter–enhancer loops required for murine hematopoietic stem and progenitor cell function. Nature Communications. doi.org/10.1038/s41467-020-20282-1.