Growth-regulated co-occupancy of Mediator and Lsm3 at intronic ribosomal protein genes

Abdel-Fattah, Wael R.Umeå universitet,Institutionen för medicinsk kemi och biofysik (författare)

Mediator is a well-known transcriptional co-regulator and serves as an adaptor between gene-specific regulatory proteins and RNA polymerase II. Studies on the chromatin-bound form of Mediator revealed interactions with additional protein complexes involved in various transcription-related processes, such as the Lsm2–8 complex that is part of the spliceosomal U6 small nuclear ribonucleoprotein complex. Here, we employ Chromatin Immunoprecipitation sequencing (ChIP-seq) of chromatin associated with the Lsm3 protein and the Med1 or Med15 Mediator subunits. We identify 86 genes co-occupied by both Lsm3 and Mediator, of which 73 were intron-containing ribosomal protein genes. In logarithmically growing cells, Mediator primarily binds to their promoter regions but also shows a second, less pronounced occupancy at their 3́-exons. During the late exponential phase, we observe a near-complete transition of Mediator from these promoters to a position in their 3́-ends, overlapping the Lsm3 binding sites ∼250 bp downstream of their last intron–exon boundaries. Using an unbiased RNA sequencing approach, we show that transition of Mediator from promoters to the last exon of these genes correlates to reduction of both their messenger RNA levels and splicing ratios, indicating that the Mediator and Lsm complexes cooperate to control growth-regulated expression of intron-containing ribosomal protein genes at the levels of transcription and splicing.

Carlsson, MattiasDepartment of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciences, Box 7026, Uppsala, Sweden (författare)
Hu, Guo-ZhenDepartment of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciences, Box 7026, Uppsala, Sweden (författare)
Singh, AjeetUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)ajsi0006 (författare)
Vergara, AlexanderUmeå universitet,Institutionen för fysiologisk botanik(Swepub:umu)alve0036 (författare)
Aslam, RameenUmeå universitet,Institutionen för medicinsk kemi och biofysik (författare)
Ronne, HansDepartment of Forest Mycology and Plant Pathology, Swedish University of Agricultural Sciences, Box 7026, Uppsala, Sweden (författare)
Björklund, StefanUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)stbj0001 (författare)
Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

Ingår i:Nucleic Acids Research: Oxford University Press52:11, s. 6220-62330305-10481362-4962

Av författaren/redakt...: Abdel-Fattah, Wa ...; Carlsson, Mattia ...; Hu, Guo-Zhen; Singh, Ajeet; Vergara, Alexand ...; Aslam, Rameen; visa fler...; Ronne, Hans; Björklund, Stefa ...; visa färre...

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