Locking for genome parasites

Credit: CC0 Public Domain

Researchers from GMI – the Gregor Mendel Institute for Molecular Biology of the Austrian Academy of Sciences – have discovered an ingenious mechanism by which Arabidopsis protects the integrity of its genome. The paper was published in a journal Biology of nature.

Is it possible for a single genetic product to silence unwanted genetic elements? Can such a strong effect be observed in the regulation of transmissible elements (TEs) or genome parasites? If yes, how does this gene product independently control transposons? A new study by Frédéric Berger’s group from GMI provides answers to these questions and dissects the mechanism of gene suppression that has long remained shrouded in mystery.

Genome parasites

Although jumping transposons promote genomic variations in the evolutionary scale, their effects on the individual organism are enormously detrimental. If not regulated, they could lead to genome instability and various diseases. In the Arabidopsis plant, a model, it has been shown that the loss of function of a single gene product identified 30 years ago, reduced DNA I methylation (DDM1), results in large and uncontrolled transposition events. DDM1 is a chromatin rearranger that helps DNA be tightly packed to silence TE, but the basic mechanism of how DDM1 silences TE is still unknown.

The arabidopsis chromatin DDM1 processor (reduced DNA I methylation) silences the transposons by binding and depositing the histone variant H2A.W, locking the transposable elements into tightly packed chromatin. Credits: FloorFour / GMI

Captured before they jump

The team around GMI group leader Frédéric Berger, with co-authors Akihis Osakabe and Bhagyshree Jamge, describes the molecular mechanism of action of DDM1. They show that DDM1 targets TE by binding H2A.W, a variant of histone H2A, one of the building blocks that coat DNA to form condensed and tightly packed heterochromatin. The team shows that deposition of H2A.W DDM1 on DNA regions rich in TE is not only necessary but also sufficient for chromatin remodeling and silencing TE. Most importantly, the team shows that this mechanism dominates with far other known mechanisms for suppressing TE in Arabidopsis and that the effect of DDM1 is specific for jumping genes with intact transposition potential, i.e. potentially mobile TE.

“Transposons integrate the genome and thus share chromatin with the host. They can be viewed as enemies hiding in houses. How do these houses differ from those that contain genes that encode proteins? The material used to build those houses is different: it contains transponds such that they cannot go out and multiply, ”says Frédéric Berger. The described attenuation mechanism does not affect the jumping gene fragments that have lost the ability to transpose themselves, nor the genes encoding the proteins. Frédéric Berger does not hesitate to describe the mechanism with a bit of humor: “It’s basically a strategy: build your enemy into blocks of special material and send him to hell!”

The arabidopsis chromatin DDM1 processor (reduced DNA I methylation) silences the transposons by binding and depositing the histone variant H2A.W, locking the transposable elements into tightly packed chromatin. Credits: FloorFour / GMI

Sent to hell, packed by DHL

The association to hell comes from ‘Hell’, the name of the human orthologist Arabidopsis DDM1. The researchers propose a new class of chromatin remodelers, grouping DDM1 and Hells along with their mouse orthologist Lsh, which they call ‘DHL’. DHL chromatin rearrangers show preserved binding sites for histone variants. In addition, all three rearrangers are associated with genomic instability and disease in their organisms, in case mutations lead to loss of their function.

DHL remodellers control transposon dynamics

DDM1 is a key factor in ‘camouflaging’ TE from transcription machines using special building blocks that prevent their recognition. Asked about the broader impact of this new mechanism, Frédéric Berger states: “DDM1 orthologists in mammals deposit a variant of the ortholog H2A.W macroH2A, which has been implicated in various human syndromes and cancers. Better insight into the mechanism of action of this class of histone-binding proteins will improve our understanding genome dynamics with influences on medicine and evolution. “

Engineering mechanisms for yeast attenuation

Frédéric Berger, who received financial assistance from 1000 Ideen for high-risk research from the Austrian Science Foundation (FWF), is already investigating the emergent properties of these histone and chromatin remodeller variants and new engineering yeast attenuation pathways based on Arabidopsis H2A.W and DDM1 .

Histone dance silences transferable elements in pluripotent stem cells

More information:
Chromatin remodel DDM1 prevents transposon mobility by precipitating the histone variant H2A.W, Biology of nature (2021). DOI: 10.1038 / s41556-021-00658-1

Provided by the Austrian Academy of Sciences

Citation: Lock for genome parasites (2021, April 8) retrieved April 8, 2021 from https://phys.org/news/2021-04-lockdown-genome-parasites.html

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