Genomic maps of lincRNA occupancy reveal principles of RNA-chromatin interactions.

Long intergenic noncoding RNAs (lincRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lincRNAs and bound protein and DNA sequences, which are enumerated by deep sequencing. ChIRP-seq of two lincRNAs reveal that RNA binding sites in the genome are focal, sequence-specific, and numerous. Human telomerase RNA TERC occupies telomeres and Wnt pathway genes. HOTAIR lincRNA preferentially binds a GA-rich homopurine DNA motif to nucleate broad domains of Polycomb occupancy and histone H3 lysine 27 trimethylation. HOTAIR occupancy occurs independently of EZH2, defining the order of RNA guidance of Polycomb occupancy. ChIRP-seq is readily applicable to numerous RNAs in different cell types and biological states, thus enabling the study of RNA regulation of chromatin and gene expression at a genomic scale. Overall design: Examination of 3 lincRNAs in 5 cell types