DNA discovery reveals key 'accordion effect' of genes shutting down

The discovery expands our understanding of how we turn genes on and off to make the different types of cells in our body as we develop in the womb

It also provides a new way to use gene silencing in the future to treat or reverse the development of a range of diseases, including cancer, congenital diseases and infectious diseases

Gene silencing is determined by how tightly the DNA is attached to the cell

The research was published in the journal Nature Communications

all in DNA

The DNA that makes up our genetic material is tightly wound around proteins, like thread is wound around a spool

In the new study, the researchers found that to turn off a gene, the DNA package must first be loosened and then tightly compressed

Professor Marnie Blewitt said the discovery of the accordion-like trigger took the team by surprise, changing their fundamental understanding of this crucial process so far

"We were surprised to find that the DNA first needs to relax in order to trigger this process," she said

"Just as an accordion needs to be opened before it can be compressed to make a note, we found that our DNA needs to be opened first before it can be compressed and genetically silenced

the power of silence

Dr Andrew Keniry says gene silencing has amazing therapeutic potential

"If we can know exactly how to turn off genes, we may one day be able to turn off harmful genes in a variety of diseases," Dr.

"For example, if you can turn off oncogenes that cause cancer, you could potentially have new treatments

"To be able to realize this dream, we first need to know how this process happens so it can be simulated with drugs, and our discovery is a much more important piece of the puzzle

The focus of basic mechanism research is to efficiently search for new factors involved in the gene silencing process

To achieve this, the team created a system they call "Christmas," based on red and green labels that are usually turned off during development

The study revealed a new molecular mechanism for gene silencing, and the researchers pinpointed the protein complex required for this process, called the BAF complex

The next steps in the research will investigate why the accordion effect is necessary for gene silencing, and how this process correlates with genes on other chromosomes, such as autosomes
.

Andrew Keniry, Natasha Jansz, Linden J.
Gearing, Iromi Wanigasuriya, Joseph Chen, Christian M.
Nefzger, Peter F.
Hickey, Quentin Gouil, Joy Liu, Kelsey A.
Breslin, Megan Iminitoff, Tamara Beck, Andres Tapia del Fierro, Lachlan Whitehead, Andrew Jarratt, Sarah A.
Kinkel, Phillippa C.
Taberlay, Tracy Willson, Miha Pakusch, Matthew E.
Ritchie, Douglas J.
Hilton, Jose M.
Polo, Marnie E.
Blewitt.
BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation .
Nature Communications , 2022; 13 (1)