Genome turned off in CLASSY gene diversifies epigenomes

Researchers from Salk Institute for Biological Studies (SIBS) have discovered that the CLASSY gene family regulates which parts of the genome are turned off in a tissue-specific manner.

What is a genome?

A genome is responsible for what parts of each cell is working at any given time, and the parts of the genome that are turned on or off in each cell or tissue play an important role in regulating the growth and development of each cell.

The CLASSY gene

The CLASSY genes essentially control where the genome is marked by DNA methylation, which is the addition of methyl chemical groups to the DNA that act like tags saying, ‘turn off.’ DNA methylation exists across diverse organisms, including plants and animals, and as a result this research has broad implications for both agriculture and medicine. This study was published in Nature Communications on 11 January 2022 and identifies the CLSY genes as major factors underlying epigenetic diversity in plant tissues.

Julie Law, senior author and associate professor in Salk’s Plant Molecular and Cellular Biology Laboratory explained: “There have been many observations that one cell or tissue type has a different DNA methylation pattern than another, but how the methylation pathways are modulated to end up with different outcomes in different tissues has remained poorly understood.

“We found that which CLSYs are expressed in a given tissue is the mechanism controlling how the core DNA methylation machinery is directed to different genomic locations in different tissues.”

DNA methylation

This study of DNA methylation falls under the field of epigenetics, which are molecular modifications that change how the DNA functions without changing the DNA sequence itself. It is considered both a necessary process and a dangerous one. This is because, while it helps to establish cell identity in a developing embryo, it can also cause cancer later in life. In plants, defects in DNA methylation can cause developmental defects and negatively impact crop yields.

DNA methylation is regulated by many factors, including certain types of small RNAs. Working with the model plant Arabidopsis thaliana, the Salk team discovered that the CLASSY gene family (CLSY 1–4) acts at different locations within the genome, depending on the tissue. This reveals that diverse patterns of methylation are generated during plant development.

This current study is an expansion on a previous study conducted by Law and her team; they found that in Arabidopsis, the CLSY genes determine which sites in the genome are methylated, via small RNAs. The present study addresses the larger question of whether this process can result in different methylation patterns in different Arabidopsis tissues, such as the leaf, flower bud, ovule, and rosette.

The team of researchers found that the CLSY genes were expressed differently depending on the plant tissue type. For example, all four of the CLSY genes were expressed in flower buds, while the CLSY3 was strongly expressed in ovules and the CLSY1 was expressed in leaf and rosette tissues.

The researchers then compared plants with mutant CLSY genes against wild-type plants. They found that depending on the tissue, different combinations of CLSY family members, or even individual CLSY proteins, controlled small RNA and DNA methylation patterns at thousands of sites throughout the genome. These findings demonstrate the CLSY genes’ role in shaping the tissues’ epigenetic landscape.

The team’s discoveries may open the door to advances in many areas, from boosting crop yields in plants to informing precision medicine in humans. “Before knowing how a diversity of DNA methylation patterns was generated during development, we didn’t have the ability to manipulate that system. Finding that the CLSY’s control methylation in a tissue-specific manner represents a major advance as it provides scientists a way to alter DNA methylation patterns with much higher precision,” concluded Law.

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