Researchers fill final gaps in Arabidopsis genome sequence

Researchers fill final gaps in Arabidopsis genome sequence

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Arabidopsis thaliana plant. Credit: Wikipedia.

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Arabidopsis thaliana plant. Credit: Wikipedia.

Arabidopsis thaliana is a species grown worldwide for genetic research purposes and was the first plant to have a complete sequence of its entire set of chromosomes (genome).

The initial genome sequence, released in 2000, had numerous gaps, but technological improvements in the years that followed closed the gaps, one by one, until only two remained: large, uncharacterized regions on chromosomes 2 and 4 where genes duplicated. RNA encodes a ribosome. In hundreds of copies.

These rRNA gene clusters, known as nucleosome organizing regions (NORs), are not only difficult to define in Arabidopsis; There are still gaps in NORs in the genome sequences of almost all eukaryotes (organisms whose cells contain a nucleus), including humans. This has hampered studies of NORs, the genes within them that encode ribosomes, the protein-synthesis machines in all living cells.

Ribosomal RNA genes are regulated in ways that are not fully understood. For example, they are known to be under epigenetic control, meaning they can be turned on or off in a way that does not depend on their sequence, but it is not clear how. Gene misregulation occurs in many types of cancer.

As a result, understanding ribosomal RNA gene regulation has long been a focus of funding for biomedical research, which includes studies in plants, yeast, fruit flies, mice, and other model organisms.

A new study published in Advancement of science, reports the complete sequence of NORs from Arabidopsis and how active and silent ribosomal RNA genes are distributed throughout the NORs. This paper was authored by postdoctoral researchers Dallin Fultz, Anastasia McKinley, and Ramia Inganti in the laboratory of Craig S. Pickard, a Howard Hughes Medical Institute scholar and distinguished professor, and the Carlos O. Miller Professor in the Departments of Biology and Medicine. Molecular and Cellular Biochemistry at Indiana University Bloomington (IUB). Previous studies by the laboratory have shown that active and silent RNA gene subtypes coexist but are associated with different NORs, based on genetic testing.

The new study identified more than 70 different gene subtypes, based on subtle differences, that are located in either NOR2 or NOR4, but not in both. By knowing the physical positions of each of these subtypes, the researchers ran tests to determine whether each subtype was turned on, producing ribosomal RNA, or turned off. They also tested what happens in genetic mutants that are unable to silence their rRNA genes.

What they found is that one NOR is almost completely silenced in developing plants, while the other NOR accounts for almost all of the ribosomal RNA gene activity – but only in its central region. Regions of high gene activity have been found to be associated with regions where chemical modification of DNA (by addition of single carbon methyl groups) is low and where neighboring genes tend to be of the same subtype.

The results provide a first glimpse into how RNA genes are organized and regulated in the context of complete NORs. Because NORs also vary in activity in other species, including humans and fruit flies, plant studies provide insights of broad biomedical importance. The studies also pave the way for future studies in Arabidopsis aimed at understanding the epigenetic control and evolution of NOR, especially the newly identified relationship between gene activity and gene subtype homology.

more information:
Dallin Foltz et al., Sequences and epigenetic landscapes of active and silent nucleation regulatory regions in Arabidopsis, Advancement of science (2023). doi: 10.1126/sciadv.adj4509

Magazine information:
Advancement of science

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