Tyrosine-1 of RNAPII CTD controls global termination of gene transcription in mammals

The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in antisense direction of promoters as well as in 3' direction several hundred kb downstream of genes. The YFFF mutant shows reduced Pol II at promoter-proximal pause sites, a loss of interaction with the Mediator and Integrator complexes and impaired recruitment of these complexes to chromatin. Consistent with these observations, Pol II loading at enhancers and maturation of snRNAs are altered in the YFFF context genome wide. We conclude that tyrosine1 residues of the CTD control termination of transcription by Pol II. Overall design: This study was performed in a human Raji cell line. It contains ChIP-seq data for RNA Pol II, H3K4me1, H3K4me3, H3K27ac, RNA-seq data for Total RNA, polyA-RNA, nascent RNA and MNase-seq data. All sequencing were performed in paired-end sequencing runs, 4 replicates for the input genomic DNA.