How to turn specific genes on and off
Treatment of a wide range of diseases may advance thanks to new
epigenetic editing technique

Date:
November 9, 2021
Source:
McGill University
Summary:
Type 1 diabetes, rheumatoid arthritis, and cancer are just some
of the disorders associated with specific genes not 'turning on'
and 'turning off' as they should. By using new CRISPR/Cas9 genome
editing technology researchers have described a new technique
that scientists across the world can potentially use to explore
novel ways of treating diseases associated with dysregulation in
DNA methylation.



FULL STORY ==========================================================================
Type 1 diabetes, rheumatoid arthritis, and cancer are just some of the disorders associated with specific genes not "turning on" and "turning
off" as they should. By using new CRISPR/Cas9 genome editing technology,
in a recent paper in Nature Communications,McGill University researchers
have described a new technique that scientists across the world can
potentially use to explore novel ways of treating diseases associated
with dysregulation in DNA methylation.


==========================================================================
All the cells in an individual's body bear the same genetic code. It is
the reading and writing of this code -- the "turning on" and "turning
off" of specific genes in specific cells -- that gives the cells their identities.

Imagine, for example, the disastrous situation wherein the genes that
encode the digestive enzymes of the stomach would be turned on in the
retinal cells of the eye and begin to devour the surrounding tissue. One
of the ways by which a cell turns off specific genes is by the reversible addition to the DNA of a minuscule chemical called a methyl group at
the precise location of that specific gene.

Scientists know that genes with more of this "DNA methylation" tend
to be "turned off" and that genes with less of this methylation tend
to be "turned on." But because until now it hasn't been possible to
manipulate the levels of DNA methylation at specific genes, there remain
many questions about what specific instances of DNA methylation do, how
they contribute to normal cellular function, and how their dysregulation contributes to disease.

In a recent study, published in Nature Communications,McGill University researchers demonstrate how they have managed to remove specific instances
of DNA methylation at specific genes in mouse and human cells grown in
culture by using CRISPR/Cas9 genome editing technology. They show that
this DNA "de- methylation" activity can be targeted to anywhere in the DNA
-- any gene of interest -- without editing the genetic code, and with no off-target activity at undesired locations in the DNA. The researchers
also describe the approaches needed to produce complete removal of DNA
methyl marks in the hopes that scientists around the world can use this
new technique to start to discover actionable instances where genes
that should be on have been turned off by DNA methylation -- such as,
for example, the insulin gene in diabetes -- and use this technique to establish new paradigms for disease treatment.

========================================================================== Story Source: Materials provided by McGill_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Daniel M. Sapozhnikov, Moshe Szyf. Unraveling the functional role
of DNA
demethylation at specific promoters by targeted steric blockage
of DNA methyltransferase with CRISPR/dCas9. Nature Communications,
2021; 12 (1) DOI: 10.1038/s41467-021-25991-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211109120326.htm

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