General Summary
The Taatjes lab investigates the molecular mechanisms by which the human transcription machinery functions and is regulated.ÌýÌýProper regulation of gene expression is fundamental to every major physiological process, and changes in gene expression patterns are hallmarks of human development and disease.ÌýÌýConsequently, the questions that we address are fundamentally important and have broad relevance to human health.Ìý
We are interested in gaining a deep understanding about the molecular mechanisms that regulate human gene expression. ÌýTo do this, we combine biochemical reconstitution experiments with biophysical, computational, and cell-based methods.ÌýÌýWe focus on the regulation of RNA polymerase II (pol II) transcription, which is governed by a host of protein factors and nucleic acid elements.ÌýÌýBecause transcriptional changes are triggered in response to extracellular cues, we also study metabolic and signaling cascades, and how they coordinately govern pol II transcription to establish an integrated cellular response. Ìý
Selected publications (recent)
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; 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.Ìý
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.Ìý
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 Oncol 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.
Johnson, JL; Yaron, TM; Huntsman, EM; Kerelsky, A; Song, J; Regev, A; Lin, T-Y; Liberatore, K; Cizin, DM; Cohen, BM; Vasan, N; Ma, Y; Krismer, K; Torres Robles, J; van de Kooij, B; van Klimmeren, AE; Andree-Busch, N; Kaufer, N; Dorovkov, MV; Ryazanov, AG; Takagi, Y; Kastenhuber, ER; Goncalves, MD; Hopkins, BD; Elemento, O; Taatjes, DJ; Maucuer, A; Yamashita, A; Degterev, A; Linding, R; Blenis, J; Hornbeck, PV; Turk, BE; Yaffe, MB; Cantley, LC. A global atlas of substrate specificities for the human serine/threonine kinome. Nature 2023, 613: 759 - 766.Ìý
Allen, BL; Quach, K; Jones, T; Levandowski, CB; Ebmeier, CC; Rubin, JD; Read, T; Dowell, RD; Schepartz, A*; Taatjes, DJ*.ÌýÌýSuppression 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; Taatjes, DJ.ÌýÌýTheÌý∆40p53 isoform inhibits p53-dependent eRNA transcription and enables regulation by signal-specific transcription factors during p53 activation.ÌýPLoS BiolÌý2021, 19: e3001364.Ìý
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; Taatjes, DJ.ÌýÌýSelective inhibition of CDK7 reveals high-confidence targets and novel mechanisms for TFIIH function in transcription.ÌýGenes DevÌý2020; 34: 1452 –Ìý1473.
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; Taatjes, DJ. TFIID enables RNA polymerase II promoter-proximal pausing.ÌýMol CellÌý2020, 78: 785 – 793.Ìý
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; Taatjes, DJ;* Kovarik, P.* Transcriptional responses to IFNgÌýrequire Mediator kinase-dependent pause release and mechanistically distinct CDK8 and CDK19 functions.Ìý Mol CellÌý2019, 76: 485 – 499.ÌýÌý
Guo, YE; Manteiga, JC; Henninger, J; Sabari, BR; Dall'Agnese, A; Hannett, NM; Spille, J-H; Afeyan, LK; Zamudio, AV;ÌýÌýShrinivas, K; Abraham, BJ; Boija, A; Decker, TM; Rimel, JK; Fant, CB; Lee, TI; Cisse, II; Sharp, PA; Taatjes, DJ; Young, RA. RNA polymerase II phosphorylation regulates a switch between transcriptional and splicing condensates.ÌýNatureÌý2019, 572: 543 – 548.
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; Taatjes, DJ;ÌýYoung, RA.ÌýTranscription factors activate genes through the phase separation capacity of their activation domains. Cell 2018, 175: 1842-1855.
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Recent 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.ÌýÌý
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.Ìý
Luyties, O; Taatjes, DJ.ÌýÌýThe Mediator kinase module: an interface between cell signaling and transcription.ÌýTrends Biochem SciÌý2022, 47: 314 - 327.ÌýÌý
Palacio, M; Taatjes DJ.ÌýMerging established mechanisms with new insights: Condensates, hubs, and the regulation of RNA polymerase II transcription.ÌýJ Mol BiolÌý2022, 433: 167216.Ìý
Schier, AC; Taatjes, DJ. Structure and mechanism of the RNA polymerase II transcription machinery.ÌýGenes Dev.Ìý2020, 34: 465 – 488.