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Mechanisms of transcription regulation in human development and disease

The Taatjes lab seeks to discoverÌýmolecular mechanisms that control human gene expression, and how transcription and signaling pathways are altered during development and disease.Ìý We focus on sequence-specific, DNA-binding transcription factors (TFs) and the Pre-Initiation Complex (PIC), whichÌýconsists of Mediator, RNA polymerase II (pol II), TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH.ÌýÌýThe PIC controls the activity of the pol II enzyme, which transcribes all protein-coding genes and most non-coding RNAs in the human genome.ÌýÌýWithin the PIC, the 1.4 MDa Mediator complex, the 1.3 MDa TFIID complex, and the 0.5 MDa TFIIH complex help regulate pol II activity in ways that remain poorly understood.ÌýÌýAt a basic level, TFIIH regulates transcription initiation and post-initiation steps (e.g. RNA processing), whereas Mediator and TFIID function by converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression).ÌýÌýWe utilize a variety of experimental techniques that include biochemical, biophysical, molecular and cell biology approaches, as well as metabolomics, proteomics, and transcriptomics.

SeeÌýÌýfor a full and up-to-date list

• Palacio M; Taatjes DJ. Real-time visualization of reconstituted transcription reveals RNA polymerase II activation mechanisms at single promoters. bioRxiv 2025, 631569.
• Luyties, O; Sanford, L; Rodino, J; Nagel, M; Jones, T; Rimel, JK; Ebmeier, CC; Palacio, M; Shelby, GS; Cozzolino, K; Brennan, F; Hartzog, A; Saucedo, MB; Watts, LP; Spencer, S; Kugel, JF; Dowell, RD; Taatjes DJ. Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3'-ends. Cell Rep 2025, 44: 115904.
• Jones, T; Feng, J; Luyties, O; Cozzolino, K; Sanford, L; Rimel, JK; Ebmeier, CC; Shelby, GS; Watts, LP; Rodino, J; Rajagopal, N; Hu, S; Brennan, F; Maas, ZL; Alnemy, S; Richter, WF; Koh, AF; Cronin, NB; Madduri, A; Das, J; Cooper, E; Hamman, KB; Chuaqui, C; Carulli, JP; Allen, MA; Spencer, S; Kotecha, A; Marineau, J; Greber, BJ; Dowell, RD; Taatjes DJ. TFIIH kinase CDK7 drives cell proliferation through a common core transcription factor network. Sci Adv 2025, 11: eadr9660.
• Cozzolino, K; Sanford, L; Hunter, S; Molison, K; Erickson, B; Courvan, MCS; Jones, T; Ajit, D; Galbraith, MG; Espinosa, JM; Bentley, DL; Allen, MA; Dowell, RD; Taatjes, DJ. Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome. eLife 2025, 13: RP100197.
• Nussbaum, DP; Martz, CA; Waters, AM; Barrera, A; Liu, A; Rutter, JC; Cerda-Smith CG; Stewart, AE; Wu, C; Cakir, M; Levandowski, CB; Kantrowitz, DE; McCall, SJ; Pierobon, M; Petricoin, EF; Smith, JJ; Reddy, TE; Der, C; Taatjes, DJ; Wood, KC. Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers. NPJ Precision Oncology 2024, 8: 124.
• Maia-Silva, D; Cunniff, PJ; Schier, AC; Skopelitis, D; Trousdell, MC; Moresco, P; Gao, Y; Kechejian, V; He, X; Sahin, Y; Wan, L; Alpsoy, A; Liverpool, J; Krainer, AR; Egeblad, M; Spector, DL; Fearon, DT; Dos Santos, CO; Taatjes, DJ; Vakoc, CR. Interaction between MED12 andÌýDNp63 activates basal identity in pancreatic ductal adenocarcinoma. Nat Genet 2024, 56: 1377 - 1385.
• Allen, BL; Quach, K; Jones, T; Levandowski, CB; Ebmeier, CC; Rubin, JD; Read, T; Dowell, RD; Schepartz, A;ÌýTaatjes, DJ.Ìý Suppression of p53 response by targeting p53–Mediator binding with a stapled peptide.ÌýCell RepÌý2022, 39: 110630.
• Levandowski, CB; Jones, T; Gruca, M; Ramamoorthy, S; Dowell, RD;ÌýTaatjes, DJ.ÌýTheÌýD40p53 isoform inhibits p53-dependent eRNA transcription and enables regulation by signal-specific transcription factors during p53 activation.ÌýPLoS BiolÌý2021, 19: e3001364.
• Rimel, JK; Poss, ZC; Erickson, B; Maas, ZL; Ebmeier, CC; Johnson, JL; Decker, T-M; Yaron, TM; Bradley, MJ; Hamman, KB; Hu, S; Malojcic, G; Marineau, JJ; White, PW; Brault, M.; Tao, L.; DeRoy, P; Clavette, C; Nayak, S; Damon, LJ; Kaltheuner, IH; Bunch, H; Cantley, LC; Geyer, M; Iwasa, J; Dowell, RD; Bentley, DL; Old WM;ÌýTaatjes, DJ.Ìý Selective inhibition of CDK7 reveals high-confidence targets and novel mechanisms for TFIIH function in transcription.ÌýGenes DevÌý2020, 34: 1452 – 1473.
• Fant, CB; Levandowski, CB; Gupta, K; Maas, ZL; Moir, JT; Rubin, JD; Sawyer, A; Esbin, M; Rimel, JK; Luyties, O; Marr, MT; Berger, I; Dowell, RD;ÌýTaatjes, DJ. TFIID enables RNA polymerase II promoter-proximal pausing.ÌýMol CellÌý2020, 78: 785 – 793.
• Guo, YE; Manteiga, JC; Henninger, J; Sabari, BR; Dall'Agnese, A; Hannett, NM; Spille, J-H; Afeyan, LK; Zamudio, AV;Ìý Shrinivas, K; Abraham, BJ; Boija, A; Decker, TM; Rimel, JK; Fant, CB; Lee, TI; Cisse, II; Sharp, PA;ÌýTaatjes, DJ; Young, RA. RNA polymerase II phosphorylation regulates a switch between transcriptional and splicing condensates.ÌýNatureÌý2019, 572: 543 – 548.
• Steinparzer, I; Sedlyarov, V; Rubin, JD; Eislmayr, K; Galbraith MD; Levandowski, CB; Vcelkova, T; Sneezum, L; Wascher, F; Amman, F; Kleinova, R; Bender, H; Andrysik, Z; Espinosa, JM; Superti-Furga, G; Dowell, RD;ÌýTaatjes, DJ; Kovarik, P.ÌýTranscriptional responses to IFNg require Mediator kinase-dependent pause release and mechanistically distinct CDK8 and CDK19 functions.ÌýMol CellÌý2019, 76: 485 – 499.

• Boija, A; Klein, IA; Sabari, BR; Dall'Agnese, A; Coffey, EL; Zamudio, AV; Li, CH; Shrinivas, K; Manteiga, J; Hannett, NM; Abraham, BJ; Schuijers, J; Afeyan, L; Guo, YE; Rimel, JK; Fant, CB; Lee, TI;ÌýTaatjes, DJ; Young, RA. Transcription factors activate genes through the phase separation capacity of their activation domains.ÌýCellÌý2018, 175: 1842 – 1855.

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Selected Review articles:

• Nagel, M; Taatjes, DJ. Regulation of RNA polymerase II transcription through re-initiation and bursting. Mol Cell 2025, 85: 1907 - 1919.
• Nayak, S; Taatjes DJ. SnapShot: Mediator Complex Structure.ÌýCellÌý2022, 185: 3458.
• Clopper, KC; Taatjes, DJ. Chemical inhibitors of transcription-associated kinases.ÌýCurr Opin Chem BiolÌý2022, 70: 102186.
• Richter, WF; Nayak, S; Iwasa, J; Taatjes, DJ. The Mediator complex as a master regulator of transcription by RNA polymerase II.ÌýNat Rev Mol Cell BiolÌý2022, 23: 732 - 749.
• Luyties, O; Taatjes, DJ.Ìý The Mediator kinase module: an interface between cell signaling and transcription.ÌýTrends Biochem SciÌý2022, 47: 314 - 327.
• Palacio, M; Taatjes DJ. Merging established mechanisms with new insights: Condensates, hubs, and the regulation of RNA polymerase II transcription.ÌýJ Mol BiolÌý2022, 433: 167216.
• Schier, AC; Taatjes, DJ. Structure and mechanism of the RNA polymerase II transcription machinery.ÌýGenes DevÌý2020, 34: 465 – 488.