Tim-Michael Decker
In higher eukaryotes, including Drosophila and mammals, RNA polymerase II (pol II) pauses 40-60 bp downstream of the transcription start site. This rate-limiting step in early elongation is referred to as promoter-proximal pausing and is observed in the majority of genes. Interestingly, pausing factors including NELF and DSIF, but also pol II itself, are subject to phosphorylation by transcriptional kinases that regulate the transcription cycle. However, the mechanistic details are poorly understood. For example, it remains unclear how specific sites of phosphorylation are functionally relevant to pol II pausing. Using an in vitro transcription system and cellular assays, I am studying the mechanisms by which different factors contribute to transcription initiation and elongation. Particularly, the actions of transcriptional kinases and their substrates are of key interest.
Publications:
Decker, T-M. Mechanisms of transcription elongation factor DSIF (Spt4-Spt5). J Mol Biol 2020, In Press. DOI: 10.1016/j.jmb.2020.09.016
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.
Klein, IA; Boija, A; Afeyan, LK; Hawken, SW; Fan, M; Dall’Agnese, A; Oksuz, O; Henninger, JE; Shrinivas, K; Sabari, BR; Sagi, I; Clark, V; Platt, J; Kar, M; McCall, P; Zamudio, AV; Manteiga, JC; Coffey, EL; Li, CH; Hannett, NM; Guo, YE; Decker, TM; Lee, TI; Zhang, T; Weng, JK; Taatjes, DJ; Chakraborty, A; Sharp, PA; Chang, YT; Hyman, AA; Gray, NS; Young, RA. Partitioning of cancer therapeutics in nuclear condensates. Science 2020, 368: 1386 – 1392.
Decker, TM; Forne, I; Straub, T; Elsaman, H; Ma, G; Shah, N; Imhof, A; Eick, D. Analog-sensitive cell line identifies cellular substrates of CDK9. Oncotarget 2019, 10: 6934 – 6943. [PMID: 31857848]
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. [PMID: 31391587]
Zamudio, AV; Dall’Agnese, A; Henninger, JE; Manteiga, JC; Afeyan, LK; Hannett, NM; Coffey, EL; Li, CH; Oksuz, O; Boija, A; Klein, IA; Sabari, BR; Hawken, SW; Spille, JH; Decker, TM; Cisse, II; Abraham, BJ; Lee, TI; Taatjes, DJ; Schuijers, J; Young, RA. Mediator condensates localize signaling factors to key cell identity genes. Mol Cell 2019, 76: 753 – 766. [PMID: 31563432]
Shah N, Maqbool MA, Yahia Y, El Aabidine AZ, Esnault C, Forné I, Decker T-M, Martin D, Schüller R, Krebs S, Blum H, Imhof A, Eick D & Andrau J-C (2018) Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals. Mol Cell 69: 48–61.
Gressel S, Schwalb B, Decker TM, Qin W, Leonhardt H, Eick D & Cramer P (2017) CDK9-dependent RNA polymerase II pausing controls transcription initiation. Elife 6: 1–24
Decker T-M, Kluge M, Krebs S, Shah N, Blum H, Friedel CC & Eick D (2017) Transcriptome analysis of dominant-negative Brd4 mutants identifies Brd4-specific target genes of small molecule inhibitor JQ1. Sci Rep 7: 1684
Schüller R, Forné I, Straub T, Schreieck A, Texier Y, Shah N, Decker T-M, Cramer P, Imhof A & Eick D (2016) Heptad-Specific Phosphorylation of RNA Polymerase II CTD. Mol Cell 61: 305–14
Arnold P, Himmels P, Weiß S, Decker T-M, Markl J, Gatterdam V, Tampé R, Bartholomäus P, Dietrich U & Dürr R (2014) Antigenic and 3D structural characterization of soluble X4 and hybrid X4-R5 HIV-1 Env trimers. Retrovirology 11: 42