Most cells share the same genetic code and yet display exquisite diversity including phenotype, function and response to stress. One thing that enables this cellular diversity is differential transcriptional programming. DNA binding proteins called transcription factors (TFs) are key players in this programming. TFs bind at regulatory regions such as enhancers that are distant from the transcriptional start site. The Mediator complex acts as a bridge that integrates signals from distal TFs to the promoter-bound RNA polymerase II enzyme. A kinase, CDK8, reversibly associates with the Mediator complex, but much remains to be uncovered about its roles in transcriptional programming. My projects focus on how CDK8 inhibition alters transcriptional regulation and TF function.
Publications
Allen, BL*; Quach, K*; Jones, T*; Levandowski, CB; Ebmeier, CC; Rubin, JD; Read, T; Dowell, RD; Schepartz, A; Taatjes, DJ. Suppression of p53 response by targeting p53–Mediator binding with a stapled peptide. Cell Rep 2022, 39: 110630.
Levandowski, CB; Jones, T; Gruca, M; Ramamoorthy, S; Dowell, RD;* Taatjes, DJ.* The ∆40p53 isoform inhibits p53-dependent eRNA transcription and enables regulation by signal-specific transcription factors during p53 activation. PLoS Biol 2021, 19: e3001364.