By employing ChIP-seq of chromatin associated with the Lsm3 subunit of the spliceosomal U6 snRNP complex and Med1 or Med15, subunits of the middle and tail modules of Mediator, respectively, we identified 86 genes co-occupied by both Lsm3 and Mediator.. Growth regulated co-occupancy of Mediator and Lsm3 at intron-containing ribosomal protein genes

By employing ChIP-seq of chromatin associated with the Lsm3 subunit of the mRNA decaysome complex (LSM-PAT) and Med1 or Med15, subunits of the middle and tail modules of Mediator, respectively, we identified 86 genes co-occupied by both Lsm3 and Mediator. Of these, 72 were identified as intron-containing ribosomal protein genes. In logarithmically growing cells, Mediator primarily binds to the promoter regions of these genes, but also shows a second, less pronounced occupancy at their 3´-exons, overlapping the binding sites for Lsm3 approximately 250 bp downstream of the last intron-exon boundaries. When cells approach stationary phase, we observe a massive transition of Mediator from the promoters to the 3´-ends of these genes. Using an unbiased RNA-seq approach we show that this transition of Mediator leads to a reduction of both transcription and splicing ratios, indicating that the Mediator and Lsm complexes co-operate to control growth-regulated expression of intron-containing ribosomal protein genes at both the levels of transcription initiation and splicing.