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Nucleosomes Stabilize ssRNA-dsDNA Triple Helices in Human Cells

Maldonado, Rodrigo, Schwartz, Uwe, Silberhorn, Elisabeth, Längst, Gernot
Molecular cell 2019 v.73 no.6 pp. 1243-1254.e6
DNA, epigenetics, gene expression, genome-wide association study, histones, humans, non-coding RNA, nucleosomes
Chromatin-associated non-coding RNAs modulate the epigenetic landscape and its associated gene expression program. The formation of triple helices is one mechanism of sequence-specific targeting of RNA to chromatin. With this study, we show an important role of the nucleosome and its relative positioning to the triplex targeting site (TTS) in stabilizing RNA-DNA triplexes in vitro and in vivo. Triplex stabilization depends on the histone H3 tail and the location of the TTS close to the nucleosomal DNA entry-exit site. Genome-wide analysis of TTS-nucleosome arrangements revealed a defined chromatin organization with an enrichment of arrangements that allow triplex formation at active regulatory sites and accessible chromatin. We further developed a method to monitor nucleosome-RNA triplexes in vivo (TRIP-seq), revealing RNA binding to TTS sites adjacent to nucleosomes. Our data strongly support an activating role for RNA triplex-nucleosome complexes, pinpointing triplex-mediated epigenetic regulation in vivo.