The Taatjes lab investigates the molecular mechanisms by which the human transcription machinery functions and is regulated.  Proper regulation of gene expression is fundamental to every major physiological process, and changes in gene expression patterns are hallmarks of human development and disease.  Consequently, the questions that we address are fundamentally important and have broad relevance to human health. 

We are interested in gaining a deep understanding about the molecular mechanisms that regulate human gene expression.  To do this, we combine biochemical reconstitution, structural, computational, and cell-based methods.  We focus on the regulation of RNA polymerase II (pol II) transcription, which is governed by a host of protein factors and nucleic acid elements.  Because 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.  

Selected 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. 

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.*  Selective inhibition of CDK7 reveals high-confidence targets and novel mechanisms for TFIIH function in transcription. Genes Dev 2020; 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; Taatjes, DJ. TFIID enables RNA polymerase II promoter-proximal pausing. Mol Cell 2020, 78: 785 – 793. 

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 IFNg require Mediator kinase-dependent pause release and mechanistically distinct CDK8 and CDK19 functions.  Mol Cell 2019, 76: 485 – 499.  

Guo, YE; Manteiga, JC; Henninger, J; Sabari, BR; Dall'Agnese, A; Hannett, NM; Spille, J-H; Afeyan, LK; Zamudio, AV;  Shrinivas, 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. Nature 2019, 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; Young, RA. Transcription factors activate genes through the phase separation capacity of their activation domains. Cell 2018, 175: 1842-1855.

Ebmeier, CC; Erickson, B; Allen, BL; Allen, MA; Kim, H; Fong, N; Jacobsen, JR; Liang, K; Shilatifard, A; Dowell, RD; Old, WM; Bentley, DL*; Taatjes, DJ*. Human TFIIH kinase CDK7 regulates transcription-associated chromatin modifications. Cell Rep. 2017, 20: 1173 - 1186.

Lerner, E; Chung, S; Allen, BL; Wang, S; Lee, JJ; Lu, SW; Grimaud, LW; Ingargiola, A; Michalet, X; Alhadid, Y; Borukhov, S; Strick, T;* Taatjes, DJ;* Weiss, S.* A backtracked and paused transcription initiation intermediate of Escherichia Coli RNA polymerase. Proc Natl Acad Sci. USA. 2016, 113: E6562 – E6571.

Poss, ZC; Ebmeier, CC; Odell, AT; Tangpeerachaikul, A; Lee, T; Pelish, HE; Shair, MD; Dowell, RD; Old, WM; Taatjes, DJ.  Identification of Mediator kinase substrates in human cells using cortistatin A and quantitative phosphoproteomics. Cell Rep. 2016, 15: 436 – 450.

Pelish, HE; Liau, BB; Nitulescu, I; Tangpeerachaikul, A; Poss, ZC; DaSilva, D; Caruso, B; Arefolov, A; Fadeyi, O; Christie, A; Du, K; Banka, D; Schneider, EV; Jestel, A; Zou, G; Si, C; Ebmeier, CC; Bronson, RT; Krivtsov, AV; Myers, AG; Kohl, N; Kung, A; Armstrong, S; Lemieux, M; Taatjes, DJ; Shair, MD. Mediator kinase inhibition further activates super-enhancer-associated genes in AML. Nature 2015, 526: 273 – 276.

Recent Review articles:

Nayak, S; Taatjes DJ. SnapShot: Mediator Complex Structure. Cell 2022, 185: 3458.

Clopper, KC; Taatjes, DJ. Chemical inhibitors of transcription-associated kinases. Curr Opin Chem Biol 2022, 70: 102186.  

Richter, WF; Nayak, S; Iwasa, J; Taatjes, DJ. The Mediator complex as a master regulator of transcription by RNA polymerase II. Nat Rev Mol Cell Biol 2022, 23: 732 - 749. 

Luyties, O; Taatjes, DJ.  The Mediator kinase module: an interface between cell signaling and transcription. Trends Biochem Sci 2022, 47: 314 - 327.  

Palacio, M; Taatjes DJ. Merging established mechanisms with new insights: Condensates, hubs, and the regulation of RNA polymerase II transcription. J Mol Biol 2022, 433: 167216. 

Schier, AC; Taatjes, DJ. Structure and mechanism of the RNA polymerase II transcription machinery. Genes Dev. 2020, 34: 465 – 488.

Fant, CB; Taatjes, DJ. Regulatory functions of the Mediator kinases CDK8 and CDK19. Transcription 2019, 10: 76 - 90.

Rimel, JK; Taatjes, DJ. The essential and multi-functional TFIIH complex. Protein Sci. 2018, 27: 1018 - 1037.

Harper, TM; Taatjes, DJ.  The complex structure and function of Mediator. J Biol Chem. 2018, 293: 13778 - 13785.

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