Transcriptional regulation and the role of diverse coactivators in animal cells

More documents

Recommendations

Info

914 R.G. Roeder / FEBS Letters 579 (2005) 909–915 (M. Guermah and R.G. Roeder, unpublished observations). Studies of the nature, functional specificity (for different activators and different histone-modifying cofactors), and mechanism of action of this factor(s) are underway. The in vitro studies of transcription activation from DNA versus chromatin templates have led to a general model [27,35,39] involving activator-dependent recruitment and function of chromatin remodeling/modifying factors followed by activator-dependent formation and function of the preinitiation complex through a mechanism(s) involving additional cofactors such as Mediator (Fig. 2). A major question concerns the mechanism(s) involved in transitions from activator-dependent chromatin remodeling/modification steps to activator-dependent PIC formation/function, especially in cases (e.g., nuclear receptors) where chromatin remodelers/ modifiers and Mediator interact with identical or overlapping surfaces (activation domains) in the activators [reviewed in 39]. The transitions could be a simple matter of equilibrium reactions, with both types of cofactors interacting with promoter bound activators within chromatin but with Mediator interactions being unproductive until chromatin remodeling/ modifying factor interactions have resulted in chromatin structural changes that facilitate subsequent Mediator interaction and PIC formation through cooperative stabilizing interactions [43]. Another appealing possibility is the involvement of additional cofactors that interact physically and functionally both with chromatin remodeling/modifying cofactors and with Mediator or PIC components. Of significance in this regard is our recent demonstration that PGC-1a, an inducible coactivator that interacts with nuclear receptors [reviewed in 71], interacts with and stimulates the function of both p300 and Mediator in nuclear receptor (PPARc)-dependent transcription [72] (Fig. 4). The PGC-1a-enhanced Mediator function is evident on DNA templates in the absence of the p300 binding site in the N-terminal region of PGC-1a. However, the effect of PGC-1a on p300-dependent transcription from a chromatin template requires both the N-terminal p300 interaction site and the C-terminal Mediator interaction site on PGC-1a, thus suggesting that the effect of PGC-1a on p300 may be linked to the effect on TRAP/Mediator. Along with the presence of multiple interaction sites between the various factors and largely non-overlapping interaction sites for PPARc, p300 and TRAP220 on PGC-1a, this suggests a model (Fig. 4) wherein PGC-1a may facilitate the transition (including cofactor exchange) between a chromatin remodeling step involving ligand-dependent binding of p300 to PPARc and a later transcription activation step involving ligand-dependent binding of TRAP/Mediator to PPARc. Itis envisioned that alternative dynamic interactions of the various components may both stabilize and enhance the function of the different complexes and, perhaps through a transient intermediate complex containing all components, facilitate the transition between them. Of significant interest is whether PGC-1a will serve as a prototype for other cofactors acting in conjunction with other transcriptional activators. Because gene activation in the cell may involve a requisite sequence of events (e.g., chromatin modifications prior to PIC formation), the use of biochemically defined systems in which partial reactions can be studied will be essential for identification and/or for elaborating the mechanism(s) of action of such cofactors. 4. Conclusions and perspectives Beginning with the discovery of the three nuclear RNA polymerases 35 years ago, biochemical (and more recently genetic) studies have identified a remarkably complex general transcription machinery and an equally complex array of coregulatory factors that facilitate functional interactions of DNA binding regulatory factors (numbering several thousand) with this machinery on corresponding target genes. This complex transcriptional apparatus appears to have evolved to facilitate the proper execution and regulation of the diverse and finely tuned gene activation pathways that are critical for normal development, cell differentiation and homeostasis. This complex apparatus allows (i) global control mechanisms for the major classes of RNA, (ii) mechanisms to activate or repress genes packaged within natural chromatin structures, (iii) multiple targets for the cooperative functions of combinations of DNA-binding regulatory factors, (iv) mechanisms for the integration of multiple signaling pathways and (v) a basis for alternative or redundant gene activation and repression pathways that may contribute to biological robustness [73]. Although they warrant extension (and validation) in more physiological assays in cell and animal models, the biochemical assays emphasized here have provided profound insights into the nature and mechanism of action of the general transcription machinery, gene specific regulatory factors, and diverse cofactors. The recent development of systems for the assembly and functional analysis of recombinant chromatin templates in biochemically defined systems, coupled with high resolution structural studies, offers the promise of an increasingly more detailed picture of the diverse events that are necessary, upon a given signal, to convert a repressed gene within a natural chromatin structure to an actively transcribed state. Acknowledgments: This work was supported by grants from the National Institutes of Health and by The Rockefeller University. I thank my colleagues for their many contributions and Sohail Malik for helpful comments on the manuscript. References [1] Roeder, R.G. (2003) Nat. Med. 9, 1239–1244. [2] Roeder, R.G. and Rutter, W.J. (1969) Nature 224, 234–237. [3] Weinmann, R. and Roeder, R.G. (1974) Proc. Natl. Acad. Sci. USA 71, 1790–1794. [4] Weinmann, R., Raskas, H.J. and Roeder, R.G. (1974) Proc. Natl. Acad. Sci. USA 71, 3426–3430. [5] Sklar, V.E.F., Schwartz, L.B. and Roeder, R.G. (1975) Proc. Natl. Acad. Sci. USA 72, 348–352. [6] Cramer, P. (2002) Curr. Opin. Struct. Biol. 12, 89–97. [7] Parker, C.S. and Roeder, R.G. (1977) Proc. Natl. Acad. Sci. USA 74, 44–48. [8] Ng, S.-Y., Parker, C.S. and Roeder, R.G. (1979) Proc. Natl. Acad. Sci. USA 76, 136–140. [9] Segall, J., Matsui, T. and Roeder, R.G. (1980) J. Biol. Chem. 255, 11986–11991. [10] Weil, P.A., Luse, D.S., Segall, J. and Roeder, R.G. (1979) Cell 18, 469–484. [11] Matsui, T., Segall, J., Weil, P.A. and Roeder, R.G. (1980) J. Biol. Chem. 255, 11992–11996. [12] Geiduschek, E.P. and Kassavetis, G.A. (2001) J. Mol. Biol. 310, 1–26. [13] Roeder, R.G. (1996) Trends Biochem. Sci. 21, 327–335. [14] Grummt, I. (2003) Genes Dev. 17, 1691–1702. [15] Lassar, A.B., Martin, P.L. and Roeder, R.G. (1983) Science 222, 740–748.
R.G. Roeder / FEBS Letters 579 (2005) 909–915 915 [16] Sawadogo, M. and Roeder, R.G. (1985) Cell 43, 165–175. [17] Van Dyke, M.W., Roeder, R.G. and Sawadogo, M. (1988) Science 241, 1335–1338. [18] Buratowski, S., Hahn, S., Guarente, L. and Sharp, P.A. (1989) Cell 56, 549–561. [19] Nikolov, D.B. and Burley, S.K. (1997) Proc. Natl. Acad. Sci. USA 94, 15–22. [20] Cramer, P., Bushnell, D.A. and Kornberg, R.D. (2001) Science 292, 1863–1876. [21] Engelke, D.R., Ng, S.-Y., Shastry, B.S. and Roeder, R.G. (1980) Cell 19, 717–728. [22] Ginsberg, A.M., King, B.O. and Roeder, R.G. (1984) Cell 39, 479–489. [23] Miller, J., McLachlan, A.D. and Klug, A. (1985) EMBO J. 4, 1609–1614. [24] Klug, A. (1999) J. Mol. Biol. 293, 215–218. [25] Rhodius, V.A. and Busby, S.J. (1998) Curr. Opin. Microbiol. 1, 152–159. [26] Patikoglou, G. and Burley, S.K. (1997) Annu. Rev. Biophys. Struct. 26, 289–325. [27] Roeder, R.G. (1998) Cold Spr. Harb. Symp. Quant. Biol. LXIII, 201–218. [28] Burley, S.K. and Roeder, R.G. (1996) Annu. Rev. Biochem. 65, 769–799. [29] Meisterernst, M., Roy, A.L., Lieu, H.M. and Roeder, R.G. (1991) Cell 66, 981–993. [30] Flanagan, P.M., Kelleher 3rd, R.J., Sayre, M.H., Tschochner, H. and Kornberg, R.D. (1991) Nature 350, 436–438. [31] Malik, S., Gu, W., Wu, W., Qin, J. and Roeder, R.G. (2000) Mol. Cell 5, 753–760. [32] Kim, Y.J., Bjorklund, S., Li, Y., Sayre, M.H. and Kornberg, R.D. (1994) Cell 77, 599–608. [33] Thompson, C.M., Koleske, A.J., Chao, D.M. and Young, R.A. (1993) Cell 73, 1361–1375. [34] Fondell, J.D., Ge, H. and Roeder, R.G. (1996) Proc. Natl. Acad. Sci. USA 93, 8329–8333. [35] Yuan, C.-X., Ito, M., Fondell, J.D., Fu, Z.-Y. and Roeder, R.G. (1998) Proc. Natl. Acad. Sci. USA 95, 7939–7944. [36] Zhu, Y., Qi, C., Jain, S., Rao, M.S. and Reddy, J.K. (1997) J Biol. Chem. 272, 25500–25506. [37] Ge, K., Guermah, M., Yuan, C.-X., Ito, M., Wallberg, A., Spiegelman, B.M. and Roeder, R.G. (2002) Nature 417, 563– 567. [38] Malik, S., Guermah, M., Yuan, C.-X., Wu, W., Yamamura, S. and Roeder, R.G. (2004) Mol. Cell. Biol. 24, 8244–8254. [39] Glass, C.K. and Rosenfeld, M.G. (2000) Genes Dev. 14, 121–141. [40] Ito, M., Yuan, C.-X., Okano, H.J., Darnell, R.B. and Roeder, R.G. (2000) Mol. Cell 5, 683–693. [41] Malik, S. and Roeder, R.G. (2000) Trends Biochem. Sci. 25, 277– 283. [42] Holstege, F.C., Jennings, E.G., Wyrick, J.J., Lee, T.I., Hengartner, C.J., Green, M.R., Golub, T.R., Lander, E.S. and Young, R.A. (1998) Cell 95, 717–728. [43] Ito, M. and Roeder, R.G. (2001) Trends Endocrin. Met. 12, 127– 134. [44] Stevens, J.L., Cantin, G.T., Wang, G., Shevchenko, A., Shevchenko, A. and Berk, A.J. (2002) Science 296, 755–758. [45] Malik, S., Baek, H., Wu, W. and Roeder, R.G. (200). Mol. Cell. Biol. In press. [46] Cosma, M.P., Panizza, S. and Nasmyth, K. (2001) Mol. Cell. 7, 1213–1220. [47] Park, J.M., Werner, J., Kim, J.M., Lis, J.T. and Kim, Y.J. (2001) Mol. Cell. 8, 9–19. [48] Baek, H.J., Malik, S., Qin, J. and Roeder, R.G. (2002) Mol. Cell. Biol. 22, 2842–2852. [49] Mittler, G., Kremmer, E., Timmers, H.T. and Meisterernst, M. (2001) EMBO Rep 2, 808–813. [50] Yudkovsky, N., Ranish, J.A. and Hahn, S. (2000) Nature 408, 225–229. [51] Samuelsen, C.O., Baraznenok, V., Khorosjutina, O., Spahr, H., Kieselbach, T., Holmberg, S. and Gustafsson, C.M. (2003) Proc. Natl. Acad. Sci. USA 100, 6422–6427. [52] Davis, J.A., Takagi, Y., Kornberg, R.D. and Asturias, F.A. (2002) Mol. Cell. 10, 409–415. [53] Taatjes, D.J., Naar, A.M., Andel 3rd, F., Nogales, E. and Tjian, R. (2002) Science 295, 1058–1062. [54] Kornberg, R.D. and Lorch, Y. (1999) Cell 98, 285–294. [55] Workman, J.L. and Roeder, R.G. (1987) Cell 51, 613–622. [56] Lorch, Y., LaPointe, J.W. and Kornberg, R.D. (1987) Cell 49, 203–210. [57] Knezetic, J.A. and Luse, D.S. (1986) Cell 45, 95–104. [58] Han, M. and Grunstein, M. (1988) Cell 55, 1137–1145. [59] Strahl, B.D. and Allis, C.D. (2000) Nature 403, 41–45. [60] Vaquero, A., Loyola, A. and Reinberg, D. (2003) Sageke.sciencemag.org/cgi/content/full/sageke;2003/14/re4. [61] Lachner, M. and Jenuwein, T. (2002) Curr. Opin. Cell. Biol. 14, 286–298. [62] Berger, S.L. (2002) Curr. Opin. Genet. Dev. 12, 142–148. [63] Brownell, J.E., Zhou, J., Ranalli, T., Kobayashi, R., Edmondson, D.G., Roth, S.Y. and Allis, C.D. (1996) Cell 84, 843–851. [64] Taunton, J., Hassig, C.A. and Schreiber, S.L. (1996) Science 272, 408–411. [65] Gu, W. and Roeder, R.G. (1997) Cell 90, 595–606. [66] An, W., Palhan, V.B., Karymov, M.A., Leuba, S.H. and Roeder, R.G. (2002) Mol. Cell 9, 811–821. [67] Ito, T., Bulger, M., Pazin, M.J., Kobayashi, R. and Kadonaga, J.T. (1997) Cell 90, 145–155. [68] Luger, K., Rechsteiner, T.J., Flaus, A.J., Waye, M.M. and Richmond, T.J. (1997) J. Mol. Biol. 272, 301–311. [69] An, W., Kim, J. and Roeder, R.G. (2004) Cell 117, 735–748. [70] Lusser, A. and Kadonaga, J.T. (2003) Bioessays 25, 1192–1200. [71] Puigserver, P. and Spiegelman, B.M. (2003) Endocr. Rev. 24, 78– 90. [72] Wallberg, A.E., Yamamura, S., Malik, S., Spiegelman, B.M. and Roeder, R.G. (2003) Mol. Cell 12, 1137–1149. [73] Kitano, H. (2004) Nat. Rev. Genet. 5, 826–837.
Page 1 and 2: FEBS 29150 FEBS Letters 579 (2005)
Page 3 and 4: R.G. Roeder / FEBS Letters 579 (200
Page 5: R.G. Roeder / FEBS Letters 579 (200

Transcriptional regulation and the role of diverse coactivators in animal cells

Create successful ePaper yourself

Delete template?

Save as template?