New study uncovers key players in gene silencing, providing fresh insights into plant growth and human diseases

Monash University

Monash University biologists have shed light on the intricate molecular mechanisms that are responsible for gene silencing induced by expanded repeats in a ground-breaking international study published in Nature Plants.

This phenomenon has been linked to a number of hereditary illnesses, including Friedreich’s ataxia in humans, and causes growth abnormalities in plants such as Arabidopsis thaliana.

The research aimed to understand the mechanism by which enlarged repeats cause epigenetic silencing, an essential procedure for controlling gene expression.

Discovering novel components that are necessary for this silencing process was accomplished by using plant model that presents the symptoms of growth defects at higher temperatures but not at lower temperatures.

SUMO protease FUG1, histone reader AL3, and chromodomain protein LHP1 were identified as the three most important actors, according to the study.

“These proteins come together to create an essential module that is required for epigenetic silencing that is induced by repeat expansion,” said lead study author Dr. Sridevi Sureshkumar, who heads the Genetics at the Core Research Group at the Monash University School of Biological Sciences.

“Our research reveals the crucial role that these proteins play in orchestrating gene silencing that is triggered by expanded repeats,” Dr Sureshkumar said.

“The awareness of these systems not only contributes to the advancement of our understanding of plant biology but also offers insights into diseases that affect humans,” she said.

During the course of the research, modern genetic screening methods and yeast two-hybrid tests were utilised in order to determine that FUG1, an uncharacterised SUMO protease, is a significant participant in epigenetic silencing. Following further analysis, it was shown that FUG1 interacts with AL3, which is a histone reader that is known to bind to particular histone marks that are related with effective gene expression.

In addition, the researchers found that AL3 protein interacts with LHP1, which is a chromodomain protein that plays a role in the dissemination of restrictive histone marks. The reversal of gene silencing and the suppression of repeat expansion-associated symptoms were both brought about by the loss of function of any one of these components during the experiment.

“These findings highlight the importance of post-translational modifiers and histone readers in epigenetic regulation,” Dr Sureshkumar said.

/Public Release.