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Dylan J. TAATJES
Office Phone: 303 492 6929
E-mail: Dylan.Taatjes@colorado.edu
FAX: 303 492 5894
Lab: Cristol Chemistry 356
Lab Phone: 303
Group Website: Taatjes Research Group
Ph.D.: University of Colorado at Boulder, 1998
Postdoctoral Fellow: University of California at Berkeley, 1999-2003
Study of large regulatory complexes
We study large, multi-subunit "Mediator" (also called CRSP and ARC-L) complexes that help regulate transcription in humans. These complexes have been isolated from human cells relatively recently and little is known regarding their mechanism of action. It is believed that CRSP and ARC-L regulate transcription by mediating signals between enhancer-bound factors and the general transcription machinery, which includes RNA polymerase II.
CRSP and ARC-L are highly related in terms of subunit composition (each share approximately 15 subunits), although ARC-L (ca. 2.0 MDa in size) possesses 4 polypeptides not present in the smaller (1.2 MDa) CRSP complex. Although both are targeted by a diverse array of regulatory proteins (Nuclear receptors, VP16, SREBP, E1A, p53, and others), only the CRSP complex appears to activate transcription; the larger ARC-L complex is inactive in vitro and may actually serve to repress activated, CRSP-dependent transcription. Electron microscopy and single-particle reconstruction has revealed that CRSP is capable of adopting dramatically different conformations. Importantly, these conformations are induced upon activator binding, generating distinct "activator-specific" conformations. Future work in the lab will address the implications of these findings. In particular, are these distinct conformational changes functionally relevant? Do they impart promoter-specific function? And how does ARC-L inhibit transcriptional activation? We hope to answer such questions using a combination of biochemical and structural techniques, in hopes of gaining insight into the mechanism of action of these large regulatory complexes.
Selected Publications
Taatjes, DJ; Marr, MT; Tjian, R. Regulatory diversity among metazoan co- activator complexes. Nat Rev Mol Cell Biol. 2004, 5, 403-410.
Taatjes, DJ; Schneider-Poetsch, T; Tjian, R. Distinct conformational states of nuclear receptor-bound CRSP–Med complexes. Nat Struct Mol Biol. 2004, 11, 664- 671.
Taatjes, DJ; Tjian, R. Structure and function of CRSP/Med2: a promoter- selective transcriptional coactivator complex. Mol Cell. 2004, 14, 675-683.
Näär, AM;Taatjes, DJ; Zhai, W; Tjian, R. Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation. Genes Dev. 2002, 16, 1339-1344.
Taatjes, DJ; Näär, AM; Andel, F; Nogales, E; Tjian, R. Structure, function, and activator-induced conformations of the CRSP coactivator. Science 2002, 295, 1058-1062.
Dernell, WS; Powers, BE; Taatjes, DJ; Cogan, P; Gaudiano, G; Koch, TH. Evaluation of the epidoxorubicin-formaldehyde conjugate, Epidoxoform, in a mouse mammary carcinoma model. Cancer Invest. 2002, 20, 712-723.
Taatjes, DJ; Koch, TH. Nuclear targeting and retention of anthracycline antitumor drugs in sensitive and resistant tumor cells. Curr. Med. Chem. 2001, 8, 15-29.
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