Study finds gene family that regulates tissue-specific DNA methylation patterns

What are the factors that determine the regulation of a cell’s genome to guarantee adequate growth and development? It turns out that the sections of the genome that are switched on or off in each type of cell or tissue play a big factor here.

According to researchers at Salk, the CLASSY gene family controls which portions of the genome are turned off in a tissue-specific manner.

The plant Arabidopsis thaliana. Image Credit: Salk Institute.

The CLASSYs fundamentally control where DNA methylation—the insertion of methyl chemical groups to DNA that act as “turn off” tags—marks the genome. Although DNA methylation occurs in a wide range of creatures, including plants and animals, this study has far-reaching implications for agriculture and medicine.

The study, which was published in Nature Communications on January 11^th, 2022, identifies the CLSY genes as important players in underlying epigenetic variability in plant tissues.

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.”

Julie Law, Study Senior Author and Associate Professor, Plant Molecular and Cellular Biology Laboratory, Salk Institute

DNA methylation is studied as part of epigenetics, which is the study of molecular alterations to DNA that influence how it operates without changing the DNA sequence. It is indeed both a necessary and risky process. It can, for example, aid in the establishment of cell identity in a developing embryo while also increasing the risk of cancer later in life. Defects in DNA methylation in plants can lead to developmental problems and lower crop yields.

DNA methylation is influenced by a variety of factors, including small RNAs. Using the model plant Arabidopsis thaliana, researchers discovered that the CLASSY gene family (CLSY 1–4) functions at different places depending on the tissue, explaining how distinct patterns of methylation are formed during plant development.

The latest discovery extends on a previous study by Law and her colleagues, where they discovered that the CLSY genes in Arabidopsis decide which locations in the genome are methylated through small RNAs. The goal of this study is to see if this mechanism can result in various methylation patterns in different Arabidopsis tissues, such as the flower bud, leaf, ovule, and rosette.

For a long time, scientists have wanted to know how different DNA methylation patterns are generated during plant development. We found different combinations of CLSY proteins are present in different tissues, which provides the opportunity to address this question.”

Ming Zhou, Study First Author and Assistant Professor, Zhejiang University

Zhou was a former postdoctoral fellow in the Law lab.

CLSY genes were found to be expressing variably depending on the plant tissue type, according to the researchers. All four CLSY genes, for example, were expressed in flower buds, while CLSY3 was highly expressed in ovules and CLSY1 was expressed in leaf and rosette tissues.

The scientists then compared plants with mutant CLSY genes to plants with wild-type plants. They discovered that various combinations of CLSY family members, or even individual CLSY proteins, dominated small RNA and DNA methylation patterns at numerous sites across the genome, depending on the tissue. These observations highlight the role of the CLSY genes in shaping the epigenetic landscape of tissues.

The findings of the team could pave the way for advancements in a variety of fields, from increasing 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 CLSYs 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.”

Julie Law, Study Senior Author and Associate Professor, Plant Molecular and Cellular Biology Laboratory, Salk Institute