Structural cell protein also directly regulates gene transcription

(Press-News.org) ITHACA, N.Y. -- A cell protein previously believed only to provide a scaffolding for DNA has also been shown to directly influence DNA transcription into RNA – the first step of the process by which an organism’s genetic code expresses itself. The fundamental breakthrough was discovered in apple cells but is relevant to all living organisms made of nucleus-containing cells, including humans.

The finding, published Dec. 20 in Plant Cell, was co-authored by Cornell researchers and colleagues from the University of California, Davis, and Shandong Agricultural University in Shandong, China.

Every cell in an organism contains its complete genetic code. But whether newly created cells help build a heart or lungs, leaves or fruit depends on how that genetic code is interpreted by specialized proteins called transcription factors.

Transcription factors are the master regulators of gene expression and are therefore highly sought after by scientists. Plant scientists can use transcription factors to target desirable traits in new crop varieties, and medical researchers can use them to develop new pharmaceuticals.

Cell proteins called linker histones were discovered in the late 1800s. They have been known to influence genetic expression by, for example, providing structure, organization and folding of DNA, but this paper is the first to demonstrate that a linker histone is also directly regulating gene expression as a transcription factor.

“In the past, people always thought that linker histones play an indirect role in regulating gene expression. This is the first case – in any species – to demonstrate that linker histones directly regulate gene expression,” said senior author Lailiang Cheng, professor in the Horticulture Section of the School of Integrative Plant Science in the College of Agriculture and Life Sciences. “Researchers working on other plants, animals and even humans might be able to use this information to identify genes targeted by linker histones that could be involved in disease development or some other important biological processes down the road.”

Cheng and his co-authors made the discovery while working to understand how sugars and acids develop in apples. Such information can help plant breeders develop new varieties, support farmers in growing their crops and improve fruit quality in storage.

In previous work, the researchers genetically manipulated apples to produce less sorbitol, the predominant sugar in leaves that is converted to fructose in fruit, and discovered that the plants also accumulated less malic acid in fruit. Both are important for apple taste and flavor.

“That prompted us to look for the molecular players linking sugars to malic acid,” Cheng said.

They used RNA sequencing to understand genetic expression of proteins important for sorbitol and malic acid accumulation in fruit and leaves, and they identified five genes that appeared to encode transcription factor proteins. One of those genes was similar to a gene known to create a linker histone protein in Arabidopsis, a plant in the mustard family that is widely used in plant biology research.

By using an Arabidopsis mutant generated at the University of Zürich in Switzerland, they demonstrated that, indeed, the gene they discovered in apples encodes a linker histone. Unexpectedly, they found that this linker histone binds to the promoter of the gene encoding a protein that transports malic acid for storage in apple cells, directly regulating its expression.

Cheng said future research could explore other genes that the linker histone may directly regulate; the function of this linker histone in other plant species to explore how similarly the proteins behave in various species; or applied research on using sorbitol to improve the flavor-enhancing malic acid in apple crops.

Da-Gang Hu, a former postdoctoral associate in Cheng’s lab and now a professor at Shandong Agricultural University, is the first author. Other Cornell contributors are Zhangjun Fei, professor at Boyce Thompson Institute; and Mengxia Zhang, Chunlong Li and Dong Meng, all postdoctoral associates in Cheng’s lab.

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