An impact of HP1γ on the fidelity of pre-mRNA splicing arises from its ability to bind RNA via intronic repeated sequences.

HP1 proteins are best known as markers of heterochromatin and gene silencing. Yet, they are also RNA-binding proteins and the HP1γ/Cbx3 family member is present on transcribed genes, together with RNA polymerase II, where it regulates co-transcriptional processes such as alternative splicing. To gain insight in the role of the RNA binding activity of HP1γ in transcriptionally active chromatin, we have captured and analyzed RNAs associated with this protein. We find that a prerequisite for RNAs to be bound by HP1γ is the presence of repeated hexameric motifs and coincidentally certain families of transposable elements. HP1γ is part of a mechanism that tethers the nascent RNA to chromatin via these repeated sequences with functional consequences on the outcome of RNA splicing reactions. Our data unveil novel determinants in the relationship between chromatin and co-transcriptional processes.