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To achieve a better understanding of these interactions, and to determine whether RNA is actually a part of the chromatin structure, the scientists developed a new technology, which they called RNA and DNA Interacting Complexes Ligated and sequenced (RADICL-seq), which maps genome-wide RNA-chromatin interactions in intact nuclei.

To test the validity of the method, the scientists looked at two non-coding RNAs which are known to be expressed preferentially in certain cell types. The first, known at NEAT1, may be involved in the structure as it is associated with a mysterious structure known as paraspeckles found in mammalian cell nuclei. The second, Fgfr2, is involved in embryonic development and tissue repair, especially for bone and blood vessels. They found that in mouse embryonic stem cells -- an early type of cell -- that NEAT1 acts almost exclusively on genomic regions of chromosome 19, from which it itself derives from, whereas in oligodendrocyte progenitor cells -- a later type of developmental cell that can differentiate into brain cells -- it interacts with a broad range of genomic regions on other chromosomes as well. Fgfr2, by contrast, mostly interacts with genomic regions on its own chromosome.

This study is a first step toward understanding how the interplay between RNA and chromatin ensures proper genome function. Our data indicate that RNAs may exert more widespread effects on gene regulation and chromatin organization than previously thought," says Alessandro Bonetti, one of the corresponding authors of the study. The broad, genome-wide applications of this technology will help us to understand the fundamental role of non-coding RNA as a regulator of genome activity, which could lead to future applications and therapies" says Piero Carninci, one of the senior authors of the study.

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