“A Profound Change in Paradigm” – Scientists Uncover New Origin Story for Key Regulatory Gene

The Polycomb repressive complicated 2 (PRC2), initially recognized in Drosophila a number of many years in the past, was discovered to be a key controller of developmental genes. Subsequent analysis revealed that PRC2 alters chromatin construction to suppress the expression of particular genes.

This preliminary understanding of PRC2’s ancestral operate — functioning primarily to regulate genes throughout growth — was challenged when it was discovered to be energetic in unicellular organisms, through which no growth takes place.

PRC2’s Ancestral Position and Evolution

A primary trace at PRC2’s unique function got here from research in crimson algae, which discovered PRC2 left its methylation mark on transposons – leaping genes that transfer across the genome. Frederic Berger and his analysis group on the Gregor Mendel Institute of Molecular Plant Biology (GMI) determined to observe this cue and, in a world collaboration with researchers at Freie Universität Berlin, College of Cambridge, Nantes College, the Nationwide Institute of Genetics (Japan) and Monash College, investigated how PRC2 acts in a spread of eukaryotes.

Over the course of evolution, PRC2’s operate shifted from repressing transposons to repressing protein-coding genes. Credit score: GMI

Investigating PRC2 Throughout Eukaryotes

To know PRC2’s function within the ancestors of eukaryotes, the researchers studied the genomes of three extensively distant lineages of eukaryotes: vegetation, SAR, and opisthokonts, the lineage to which people and fungi belong.

All of those eukaryotes comprise transposons, cell genetic parts that may excise themselves from DNA and insert at novel places – a possible menace to genome stability, therefore why transposons need to be silenced. In mutant diatoms, bryophytes, and crimson algae the removing of PRC2 exercise prompted the lack of silencing of transposable parts.

Findings and Implications

“These findings present that PRC2 represses transposable parts in these distant lineages, which defines this as a operate that arose within the ancestor of all three lineages. PRC2’s origin was more likely to primarily defend the genome from invasion by transposons. This ancestral operate is a profound change in paradigm,” says Frederic Berger, group chief at GMI and the research’s corresponding writer.

Over the course of evolution, nonetheless, the operate of PRC2 step by step shifted from repressing transposons to repressing protein-coding genes, its initially described function. In land vegetation, the researchers discover “fossil TEs” to nonetheless be targets for PRC2, which then silences genes within the neighborhood.

“In flowering vegetation, like Arabidopsis, which advanced extra just lately, remnants of TEs are nonetheless current and recruit PRC2 to silence close by genes”, explains Tetsuya Hisanaga, a postdoctoral researcher within the Berger group and the research’s first writer. “We hypothesize that in Arabidopsis, some TEs have been domesticated, turning into parts concerned in modulating protein-coding genes.”

Reference: “The Polycomb repressive complicated 2 deposits H3K27me3 and represses transposable parts in a broad vary of eukaryotes” by Tetsuya Hisanaga, Facundo Romani, Shuangyang Wu, Teresa Kowar, Yue Wu, Ruth Lintermann, Arie Fridrich, Chung Hyun Cho, Timothée Chaumier, Bhagyshree Jamge, Sean A. Montgomery, Elin Axelsson, Svetlana Akimcheva, Tom Dierschke, John L. Bowman, Takayuki Fujiwara, Shunsuke Hirooka, Shin-ya Miyagishima, Liam Dolan, Leila Tirichine, Daniel Schubert and Frédéric Berger, 21 September 2023, Present Biology.
DOI: 10.1016/j.cub.2023.08.073