Widespread RNA Binding by Chromatin Associated Proteins

Recent evidence suggests that RNA interaction can regulate the activity and localization of DNA binding proteins, particularly chromatin-associated proteins. However, it is unknown if these observations are specialized instances for a few key RNAs and chromatin factors in specific contexts, or a general mechanism underlying the establishment of chromatin state and regulation of gene expression. Here, we introduce formaldehyde RNA ImmunoPrecipitation (fRIP-Seq), a sensitive method for cataloging RNA-protein interactions, to survey the RNA associated with a panel of 24 chromatin-associated and traditional RNA binding proteins. For each protein that reproducibly bound measurable quantities of bulk RNA (90% of the panel), we detected enrichment for hundreds to thousands of both noncoding and mRNA transcripts. We found that the enriched sets of RNA share biochemical, functional, and epigenetic properties. Thus, these data provide strong evidence that non-random RNA association is a common feature across diverse classes of chromatin modifying complexes. Overall design: RNA associated with 24 different proteins using fRIP was compared to total RNA-seq