A CTD code for RNA polymerase II promotes heterochromatin formation via lncRNA and RNAi

Some eukaryotic long non-coding RNAs (lncRNAs) regulate chromatin strucuture, but the molecular mechanism remais obscure. In fission yeast pericentromeric heterochromatin, the lncRNA transcribed by RNA polymerase II (RNAPII) co-transcriptionally associates with heterochromatin and assembles the RNA interference (RNAi) machinery to produce siRNA, which promtes the methylation of histone H3 lysine-9 (H3K9), a histone code for heterochromatin formation. The largest subunit of RNAPII has a carboxyl-terminal repeat domain (CTD) containing repeats of the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7, where differential phosphorylation of the residues (CTD codes) coordinates transcription and RNA processing. Here, we found that a phosphorylation of Ser7 directed co-transcriptional association of lncRNA with heterochromatin via the simultaneous binding of a RNA factor, Chp1 to methylated H3K9 and lncRNA. The Chp1-mediated association of lncRNA with chromatin is required for siRNA production and H3K9 methlation. These observations indicate a role for the CTD code in the regulation of histone code by lncRNAs.