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.