A novel mediator between activator proteins and the RNA polymerase II transcription apparatus
Open accessAbstract
One gene activator protein may interfere with the effects of another in eukaryotic cells. We report here that a hybrid yeast-herpes gene activator protein inhibits transcriptional activation by a thymidine-rich DNA element in yeast. This example of activator interference can be faithfully reproduced in vitro. Interference is reversed by a partially purified yeast component, but not by RNA polymerase II or various polymerase II transcription factors. We conclude that the partially purified yeast component is a novel factor, and we suggest this factor mediates the transcriptional activation process.
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At active enhancers, BRD4 co-localises with the Mediator complex, which assembles the pre-initiation complex and RNAP to initiate transcription.
“At active enhancers, the BRD4 protein co-localises with the Mediator complex, which in turn assembles the pre-initiation complex (PIC) and RNAP to initiate transcription [66–68].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [68]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · cited 2× · see citing works
“Protein was determined by the method of Bradford (1976) , using bovine serum albumin as a standard, and assays of P-galactosidase activity were performed as previously described (Miller, 1972; Guarente, 1983).”
MethodTransformation of intact yeast cells treated with alkali cations.
Ito, H., Fukuda, Y., Murata, K., & Kimura, A. (1984) · Journal of Bacteriology · doi:10.1271/bbb1961.48.341 · Cited by 4,235 · cited 1×
“Assays of BGaiactosidase Activity in Vivo Plasmid DNAs were introduced into Saccharomyces cerevisiae strain 5C (a his3-A200 ura3-52) by a lithium acetate transformation procedure (ito et al., 1983).”
MethodGAL4-VP16 is an unusually potent transcriptional activator
Sadowski, I., Ma, J., Triezenberg, S., & Ptashne, M. (1988) · Nature · doi:10.1038/335563a0 · Cited by 1,298 · cited 1× · see citing works
“…GAL4-VP16, comprising the DNA binding domain (amino acids 1-147) of GAL4 fused to the activation domain (carboxy-terminal 78 amino acids) of VP16 (Sadowski et al., 1988), and a yeast factor whose binding site is a thymidine-rich sequence from upstream of the DED7 gene (T-rich binding factor; Lue…”
MethodYeast promoters and lacZ fusions designed to study expression of cloned genes in yeast.
Guarente, L. P. (1983) · Methods in Enzymology · doi:10.1016/0076-6879(83)01013-7 · Cited by 1,022 · cited 1× · see citing works
“Protein was determined by the method of Bradford (1976), using bovine serum albumin as a standard, and assays of P-galactosidase activity were performed as previously described (Miller, 1972; Guarente, 1983).”
MethodSawadogo, M., & Roeder, R. (1985) · Cell · doi:10.1016/0092-8674(85)90021-2 · Cited by 925 · cited 3× · see citing works
“One line of evidence comes from alterations in the DNAase I footprint of partially purified HeLa TFIID on the adenovirus major late and E4 promoters caused by activator protein binding (Sawadogo and Roeder, 1985b; Horikoshi et al., 1988a, 1988b).”
BackgroundTriezenberg, S., Kingsbury, R., & McKnight, S. (1988) · Genes & Development · doi:10.1101/gad.2.6.718 · Cited by 785 · cited 1× · see citing works
“For example, herpes viral protein 16 (VP16), an activator of immediate early gene expression in herpes virus-infected cells, causes a severalfold reduction in the level of transcription of an unrelated gene (Triezenberg et al., 1988).”
BackgroundA new class of yeast transcriptional activators.
Ma, J., & Ptashne, M. (1987) · Cell · doi:10.1016/0092-8674(87)90015-8 · Cited by 660 · cited 2× · see citing works
“A single copy plasmid for expression of GAL4VP16 from the ADH7 plromoter, pCEN4:G4VPlG, was created by the insertion of the Kpnl fragment containing CEN4 sequences from pCZA into the unique Xbal site of pMA424 (gift of J. Ma and M. Ptashne; Ma and Ptashne, 1987) by blunt end ligation, leaving the 2pm origin intact but…”
MethodNegative effect of the transcriptional activator GAL4
Gill, G., & Ptashne, M. (1988) · Nature · doi:10.1038/334721a0 · Cited by 648 · cited 1× · see citing works
“Similarly, high levels of the activator GAL4 in yeast cells diminish expression of genes lacking GAL4 binding sites as much as 5fold (Gill and Ptashne, 1988).”
BackgroundSteroid hormone receptors compete for factors that mediate their enhancer function.
Meyer, M., Gronemeyer, H., Turcotte, B., Bocquel, M., Tasset, D., & Chambon, P. (1989) · Cell · doi:10.1016/0092-8674(89)90918-5 · Cited by 542 · cited 2× · see citing works
“In the case of the vertebrate estrogen, progesterone, and glucocorticoid receptors, which activate responsive genes in the presence of hormone, various pairwise combinations of both transfected and endogenous receptor genes exhibit interference in a hormone-dependent fashion (Meyer et al., 1989).”
BackgroundBuchman, A., Kimmerly, W. J., Rine, J., & Kornberg, R. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.1.210-225.1988 · Cited by 456 · cited 6× · see citing works
“A similar inhibition of activation by the GRFI binding EN07 UAS was observed.”
BackgroundInfluentialSelf-citationSawadogo, M., & Roeder, R. G. (1985) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.82.13.4394 · Cited by 421 · see citing works
Struhl, K. (1985) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.82.24.8419 · Cited by 404 · cited 1× · see citing works
“Possibly, the factor that binds to this element has a higher affinity than GAL4-VP16 for the component mediating activation, or alternatively, this element may activate transcription by a different mechanism (Struhl, 1985).”
BackgroundHorikoshi, M., Hai, T., Lin, Y.-S., Green, M. R., & Roeder, R. (1988) · Cell · doi:10.1016/0092-8674(88)90118-3 · Cited by 354 · cited 2× · see citing works
“One line of evidence comes from alterations in the DNAase I footprint of partially purified HeLa TFIID on the adenovirus major late and E4 promoters caused by activator protein binding (Sawadogo and Roeder, 1985b; Horikoshi et al., 1988a, 1988b).”
BackgroundFunction of a yeast TATA element-binding protein in a mammalian transcription system
Buratowski, S., Hahn, S., Sharp, P., & Guarente, L. (1988) · Nature · doi:10.1038/334037a0 · Cited by 275 · cited 2× · see citing works
“A yeast TATA binding protein purified according to published methods (Buratowski et al., 1988) and purified yeast RNA polymerase II (Edwards et al.”
MethodBerger, S., Cress, W., Cress, A., Triezenberg, S., & Guarente, L. (1990) · Cell · doi:10.1016/0092-8674(90)90684-7 · Cited by 271 · cited 1× · see citing works
“This observation of inhibition by GAL4-VP16 in vitro has been confirmed by others (Berger et al., 1990).”
ResultBuchman, A., Lue, N., & Kornberg, R. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.12.5086-5099.1988 · Cited by 256 · cited 6×
“A similar inhibition of activation by the GRFI binding EN07 UAS was observed.”
BackgroundInfluentialSelf-citationHorikoshi, M., Carey, M. F., Kakidani, H., & Roeder, R. (1988) · Cell · doi:10.1016/s0092-8674(88)80011-4 · Cited by 231 · cited 1× · see citing works
“One line of evidence comes from alterations in the DNAase I footprint of partially purified HeLa TFIID on the adenovirus major late and E4 promoters caused by activator protein binding (Sawadogo and Roeder, 1985b; Horikoshi et al., 1988a, 1988b).”
BackgroundFedor, M. J., Lue, N., & Kornberg, R. (1988) · Journal of Molecular Biology · doi:10.1016/0022-2836(88)90603-1 · Cited by 220 · cited 1× · see citing works
“(The slight activity of the GAL70 UAS in the absence of GAL4-VP16 may be due to incomplete catabolite repression of endogenous GAL4 function in this yeast strain, or to the recognition of the UAS sequence by other factors [Fedor et al., 1988; Chasman et al., 19901.)”
BackgroundSelf-citationReinberg, D., Horikoshi, M., & Roeder, R. G. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61506-6 · Cited by 210 · cited 2× · see citing works
“Similar experiments were performed with HeLa TFIIA, TFIIB, TFIID, and TFllElF (Reinberg et al., 1987) and with rat liver transcription factors a, Pr, 6, E, and T (Conaway et al.”
MethodChasman, D. I., Lue, N. F., Buchman, A. R., LaPointe, J. W., Lorch, Y., & Kornberg, R. D. (1990) · Genes & Development · doi:10.1101/gad.4.4.503 · Cited by 208 · see citing works
Self-citationNucleotide sequence and transcriptional mapping of the yeast pet56-his3-ded1 gene region.
Struhl, K. (1985) · Nucleic Acids Research · doi:10.1093/nar/13.23.8587 · Cited by 183 · cited 3× · see citing works
“Possibly, the factor that binds to this element has a higher affinity than GAL4-VP16 for the component mediating activation, or alternatively, this element may activate transcription by a different mechanism (Struhl, 1985).”
BackgroundActivation of yeast polymerase II transcription by herpesvirus VP16 and GAL4 derivatives in vitro
Chasman, D. I., Leatherwood, J. K., Carey, M. F., Ptashne, M., & Kornberg, R. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.11.4746-4749.1989 · Cited by 154 · cited 3× · see citing works
“(C) Transcription of p(DED48)aCG- as in (A) in the presence of 100 ng of the GAL4 binding oligonucleotide 3GALlO (solid diamonds) (Chasman et al., 1989) or a control oligonucleotide, SPT2 (dotted open squares) (Buchman and Kornberg.”
MethodInfluentialSelf-citationBuchman, A., & Kornberg, R. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.3.887-897.1990 · Cited by 126 · cited 2×
“, 1988), and a yeast factor whose binding site is a thymidine-rich sequence from upstream of the DED7 gene (T-rich binding factor; Lue et al., 1989a; Buchman and Kornberg, 1990).”
BackgroundMethodSelf-citationAccurate initiation at RNA polymerase II promoters in extracts from Saccharomyces cerevisiae.
Lue, N., & Kornberg, R. (1987) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.84.24.8839 · Cited by 110 · cited 1× · see citing works
“Preparation and Fractionation of Nuclear Extracts Yeast nuclear extracts were prepared from strain BJ926 essentially as described (Lue and Kornberg, 1987; Lue et al., 1989a), with the following modifications.”
MethodSelf-citationPurification and lipid-layer crystallization of yeast RNA polymerase II.
Edwards, A., Darst, S., Feaver, W. J., Thompson, N., Burgess, R., & Kornberg, R. (1990) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.87.6.2122 · Cited by 97 · cited 4×
“5 mglml) was purified by procedures that maintained the integrity of the largest subunit (Edwards et al., 1990).”
MethodInfluentialSelf-citationCopy number control by a yeast centromere.
Tschumper, G., & Carbon, J. (1983) · Gene · doi:10.1016/0378-1119(83)90054-9 · Cited by 94 · cited 2× · see citing works
“Ptashne; Ma and Ptashne, 1987) by blunt end ligation, leaving the 2pm origin intact but imposing centromteric regulation of copy number (Tschumper and Carbon, 1983).”
BackgroundActivation of yeast RNA polymerase II transcription by a thymidine-rich upstream element in vitro.
Lue, N., Buchman, A., & Kornberg, R. (1989) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.86.2.486 · Cited by 90 · cited 10× · see citing works
“…there was little effect of the GAL70 UAS, and the fNO7, DED7, and d(T)s9 UAS elements stimulated expression to the same extent as reported previously (compare levels of 6-galactosidase activity for these UAS elements and that for no UAS in Table 1; Buchman et al., 1988b; Lue et al., 1989a).”
BackgroundMethodInfluentialSelf-citationInitiation by yeast RNA polymerase II at the adenoviral major late promoter in vitro.
Lue, N., Flanagan, P., Sugimoto, K., & Kornberg, R. (1989) · Science · doi:10.1126/science.2510298 · Cited by 61 · cited 9× · see citing works
“…there was little effect of the GAL70 UAS, and the fNO7, DED7, and d(T)s9 UAS elements stimulated expression to the same extent as reported previously (compare levels of 6-galactosidase activity for these UAS elements and that for no UAS in Table 1; Buchman et al., 1988b; Lue et al., 1989a).”
BackgroundMethodInfluentialSelf-citationResolution of factors required for the initiation of transcription by yeast RNA polymerase II.
Flanagan, P., Kelleher, R., Feaver, W. J., Lue, N., LaPointe, J. W., & Kornberg, R. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38563-1 · Cited by 46 · cited 2× · see citing works
“The amount of each purified protein tested ranged from about 0.05 to 4 times that required for maximal basal transcription in a reconstituted yeast system (Flanagan et al., 1990).”
BackgroundInfluentialSelf-citationYeast GCN4 transcriptional activator protein interacts with RNA polymerase II in vitro.
Brandl, C. J., & Struhl, K. (1989) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.86.8.2652 · Cited by 38
Conaway, J., Travis, E., & Conaway, R. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39151-3 · Cited by 9 · cited 2×
“, 1987) and with rat liver transcription factors a, Pr, 6, E, and T (Conaway et al., 1990).”
BackgroundMethodConaway, J., Reines, D., & Conaway, R. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39149-5 · Cited by 7 · cited 1×
“Similar experiments were performed with HeLa TFIIA, TFIIB, TFIID, and TFllElF (Reinberg et al., 1987) and with rat liver transcription factors a, Pr, 6, E, and T (Conaway et al., 1990).”
Flagged first, then by citations
3 of the 35 references couldn’t be matched to a known paper.
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Kim, Y.-J., Björklund, S., Li, Y., Sayre, M. H., & Kornberg, R. D. (1994) · Cell · doi:10.1016/0092-8674(94)90221-6 · Cited by 1,080 · see citing works
“A second activity, termed mediator of transcriptional activation and originally demonstrated in yeast, confers a response to activator proteins upon a system reconstituted with TBP and is distinct from all the basal factors (Kelleher et al., 1990; Flanagan et al., 1991).”
BackgroundSelf-citationDynlacht, B., Hoey, T., & Tjian, R. (1991) · Cell · doi:10.1016/0092-8674(81)90019-2 · Cited by 640 · see citing works
“…purified recombinant TBP suggest instead that activator proteins and TBP may not interact directly but require intermediary proteins, or coactivators, to promote transcriptional activation (Berger et al., 1990; Hoey et al., 1990; Kelleher et al., 1990; Peterson et al., 1990; Pugh and Tjian, 1990).”
BackgroundBRD4 and Cancer: going beyond transcriptional regulation
Donati, B., Lorenzini, E., & Ciarrocchi, A. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0915-9 · Cited by 713 · see citing works
Mediator and the mechanism of transcriptional activation
Kornberg, R. D. (2005) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.03.011 · Cited by 595 · see citing works
“However, the widespread belief in a direct mechanism was finally challenged by analysis of squelching in a crude yeast pol II transcription system in vitro [ 6 ].”
MethodSelf-citationMolecular Genetics of the RNA Polymerase II General Transcriptional Machinery
Hampsey, M. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.2.465-503.1998 · Cited by 561 · see citing works
“Evidence for a transcriptional mediator came from squelching experiments, defined by the ability of one activator to inhibit transcription by another activator (138, 244).”
BackgroundTBP, a universal eukaryotic transcription factor?Preprint
Hernandez, N. (1993) · Genes & Development · doi:10.1101/gad.7.7b.1291 · Cited by 568 · see citing works
Hoey, T., Weinzierl, R., Gill, G., Chen, J.-L., Dynlacht, B., & Tjian, R. (1993) · Cell · doi:10.1016/0092-8674(93)90664-c · Cited by 533 · see citing works
Mechanism of action of an acidic transcriptional activator in vitro.
Lin, Y.-S., & Green, M. R. (1991) · Cell · doi:10.1016/0092-8674(91)90321-o · Cited by 475 · see citing works
Mediator of transcriptional regulation.
Myers, L., & Kornberg, R. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.729 · Cited by 466 · see citing works
Self-citationPtashne, M., & Gann, A. A. F. (1990) · Nature · doi:10.1038/346329a0 · Cited by 455 · see citing works
Berger, S. L., Piña, B., Silverman, N., Marcus, G. A., Agapite, J., Regier, J. L., Triezenberg, S. J., & Guarente, L. (1992) · Cell · doi:10.1016/0092-8674(92)90100-q · Cited by 435 · see citing works
Goodrich, J., Hoey, T., Thut, C., Admon, A., & Tjian, R. (1993) · Cell · doi:10.1016/0092-8674(93)90386-5 · Cited by 417 · see citing works
Critical structural elements of the VP16 transcriptional activation domain.
Cress, W., & Triezenberg, S. (1991) · Science · doi:10.1126/science.1846049 · Cited by 414 · see citing works
The molecular basis of eukaryotic transcription
Kornberg, R. (2007) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0704138104 · Cited by 401 · see citing works
“We referred to this activity as mediator [9, 10], and in 1994, stefan björklund and young-Joon kim isolated the active protein as an assembly of more than twenty subunits, with a total mass in excess of a million Daltons [11].”
MethodSelf-citationCloning, expression, and transcriptional properties of the human enhancer factor TEF-1
Xiao, J. H., Davidson, I., Matthes, H. W. D., Garnier, J., & Chambon, P. (1991) · Cell · doi:10.1016/0092-8674(91)90088-g · Cited by 417 · see citing works
A mediator required for activation of RNA polymerase II transcription in vitro
Flanagan, P. M., Kelleher, R. J., Sayre, M. H., Tschochner, H., & Kornberg, R. D. (1991) · Nature · doi:10.1038/350436a0 · Cited by 386 · see citing works
Self-citationChen, R., Jiang, H.-L., Li, L., Zhai, Q., Qi, L.-L., Zhou, W.-K., Liu, X.-Q., Li, H., Zheng, W.-G., Sun, J.-Q., et al. (2012) · The Plant Cell · doi:10.1105/tpc.112.098277 · Cited by 380 · see citing works
DNA topoisomerase I is involved in both repression and activation of transcription
Merino, A., Madden, K., Lane, W. A. S., Champoux, J., & Reinberg, D. (1993) · Nature · doi:10.1038/365227a0 · Cited by 380 · see citing works
Baron, U., Gossen, M., & Bujard, H. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.14.2723 · Cited by 370 · see citing works
The Mediator complex and transcription regulation
Poss, Z. C., Ebmeier, C. C., & Taatjes, D. J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.840259 · Cited by 364 · see citing works
Pongubala, J. M., Nagulapalli, S., Klemsz, M. J., McKercher, S. R., Maki, R. A., & Atchison, M. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.1.368 · Cited by 354 · see citing works
Cormack, B., & Struhl, K. (1992) · Cell · doi:10.1016/0092-8674(92)90232-2 · Cited by 351 · see citing works
“TBP can function with the other basic RNA pol II initiation factors in supporting TATA-dependent transcription, but other factors (called adaptors, mediators, or coactivators) appear to be required for responding to transcriptional activator proteins (Kambadur et al., 1990; Kelleher et al., 1990; Meisterernst et al.,…”
BackgroundVidal, M., & Gaber, R. F. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.12.6317-6327.1991 · Cited by 342 · see citing works
PU.1 Recruits a Second Nuclear Factor to a Site Important for Immunoglobulin κ 3' Enhancer Activity
Pongubala, J. M. R., Nagulapalli, S., Klemsz, M. J., McKercher, S. R., Maki, R. A., & Atchison, M. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.1.368-378.1992 · Cited by 105 · see citing works
“There is, however, some evidence that activation domains may interact with TATAbinding factor TF-IID or TFIIB or with coactivator proteins (4, 18, 24, 25, 36, 40).”
BackgroundBinding of general transcription factor TFIIB to an acidic activating region
Lin, Y.-S., Ha, I., Maldonado, E., Reinberg, D., & Green, M. R. (1991) · Nature · doi:10.1038/353569a0 · Cited by 338 · see citing works
The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain.Preprint
Myers, L., Gustafsson, C., Bushnell, D., Lui, M., Erdjument-Bromage, H., Tempst, P., & Kornberg, R. (1998) · Genes & Development · doi:10.1101/gad.12.1.45 · Cited by 329 · see citing works
Self-citationCoactivators for a proline-rich activator purified from the multisubunit human TFIID complex.Preprint
Tanese, N., Pugh, B., & Tjian, R. (1991) · Genes & Development · doi:10.1101/gad.5.12a.2212 · Cited by 316 · see citing works
Purification of a plant mediator from Arabidopsis thaliana identifies PFT1 as the Med25 subunit.
Bäckström, S., Elfving, N., Nilsson, R., Wingsle, G., & Björklund, S. (2007) · Molecules and Cells · doi:10.1016/j.molcel.2007.05.007 · Cited by 308 · see citing works
A Human RNA Polymerase II Complex Containing Factors That Modify Chromatin Structure
Cho, H. K., Orphanides, G., Sun, X., Yang, X., Ogryzko, V. V., Lees, E. M., Nakatani, Y., & Reinberg, D. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.9.5355 · Cited by 277 · see citing works
Bourbon, H., Aguilera, A., Ansari, A., Asturias, F., Berk, A., Björklund, S., Blackwell, T., Borggrefe, T., Carey, M. F., Carlson, M., et al. (2004) · Molecules and Cells · doi:10.1016/j.molcel.2004.05.011 · Cited by 293 · see citing works
Self-citationThe role of Mediator in small and long noncoding RNA production in Arabidopsis thaliana
Kim, Y., Zheng, B.-L., Yu, Y., Won, S., Mo, B.-X., & Chen, X.-M. (2011) · EMBO Journal · doi:10.1038/emboj.2011.3 · Cited by 283 · see citing works
Activation of class II gene transcription by regulatory factors is potentiated by a novel activity.
Meisterernst, M., Roy, A., Lieu, H. M., & Roeder, R. (1991) · Cell · doi:10.1016/0092-8674(91)90443-3 · Cited by 281 · see citing works
Evidence for a Mediator of RNA Polymerase II Transcriptional Regulation Conserved from Yeast to Man
Boube, M., Joulia, L., Cribbs, D. L., & Bourbon, H.-M. G. (2002) · Cell · doi:10.1016/s0092-8674(02)00830-9 · Cited by 263 · see citing works
Berger, S., Cress, W., Cress, A., Triezenberg, S., & Guarente, L. (1990) · Cell · doi:10.1016/0092-8674(90)90684-7 · Cited by 271 · see citing works
Suen, C. S., Berrodin, T. J., Mastroeni, R., Cheskis, B. J., Lyttle, C. R., & Frail, D. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.42.27645 · Cited by 252 · see citing works
Commitment and activation at pol II promoters: a tail of protein-protein interactions.
Lewin, B. (1990) · Cell · doi:10.1016/0092-8674(90)90675-5 · Cited by 244 · see citing works
The Mediator complex: a master coordinator of transcription and cell lineage development
Yin, J., & Wang, G. (2014) · Development · doi:10.1242/dev.098392 · Cited by 222 · see citing works
“Mediator is a large, multisubunit complex that was discovered following efforts to understand how RNA polymerase II (Pol II)mediated transcription is regulated by transcription factors in yeast (Nonet and Young, 1989; Kelleher et al., 1990; Thompson et al., 1993; Kim et al., 1994).”
BackgroundInfluentialHistone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo
Candau, R., Zhou, J., Allis, C. D., & Berger, S. L. (1997) · The EMBO Journal · doi:10.1093/emboj/16.3.555 · Cited by 213 · see citing works
The RNA polymerase II elongation complex
Aso, T., Conaway, J., & Conaway, R. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.14.7589983 · Cited by 227
Roberts, S., Ha, I., Maldonado, E., Reinberg, D., & Green, M. R. (1993) · Nature · doi:10.1038/363741a0 · Cited by 222 · see citing works
The yeast Mediator complex and its regulation.
Björklund, S., & Gustafsson, C. (2005) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/j.tibs.2005.03.008 · Cited by 221 · see citing works
Dysregulation of the basal RNA polymerase transcription apparatus in cancer
Bywater, M. J., Pearson, R. B., McArthur, G. A., & Hannan, R. D. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3496 · Cited by 219 · see citing works
Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein.
Mendel, D., Khavari, P., Conley, P., Graves, M. K., Hansen, L. P., Admon, A., & Crabtree, G. (1991) · Science · doi:10.1126/science.1763325 · Cited by 219 · see citing works
Kretzschmar, M., Kaiser, K., Lottspeich, F., & Meisterernst, M. (1994) · Cell · doi:10.1016/0092-8674(94)90429-4 · Cited by 214 · see citing works
Lieberman, P., & Berk, A. J. (1991) · Genes & Development · doi:10.1101/gad.5.12b.2441 · Cited by 208 · see citing works
Drosophila TAFII150: similarity to yeast gene TSM-1 and specific binding to core promoter DNA.
Verrijzer, C., Yokomori, K., Chen, J.-L., & Tjian, R. (1994) · Science · doi:10.1126/science.8178153 · Cited by 206 · see citing works
Yin-yang 1 activates the c-myc promoter
Riggs, K., Saleque, S., Wong, K., Merrell, K., Lee, J.-S., Shi, Y., & Calame, K. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.12.7487-7495.1993 · Cited by 203
“It is likely that other transcription factors which bind nearby sites or specific TATA-binding-protein-associating factors (6, 37) or other proteins (2, 19, 30) which participate in the formation of preinitiation complexes at the c-myc transcription initiation sites interact with YY1 in a way which alters its activity…”
BackgroundCandau, R., Moore, P. A., Wang, L., Barlev, N. A., Ying, C. Y., Rosen, C. A., & Berger, S. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.2.593 · Cited by 202 · see citing works
“LexA fusions to either full-length yADA2 (1-434), the amino terminus ( 1-166 ), or the carboxyl terminus (167-434) were cotransformedintoyeastcellsinthepresenceorabsenceofendogenousyGCN5.”
BackgroundMethodInfluentialBarlev, N., Candau, R., Wang, L., Darpino, P., Silverman, N., & Berger, S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.33.19337 · Cited by 197 · see citing works
Role of CDK/cyclin complexes in transcription and RNA splicing
Loyer, P., Trembley, J. H., Katona, R. L., Kidd, V. J., & Lahti, J. M. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2005.02.005 · Cited by 188 · see citing works
McEwan, I., & Gustafsson, J.-Å. (1997) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.94.16.8485 · Cited by 186 · see citing works
Transcription under the Control of Nuclear Arm/β-Catenin
Städeli, R., Hoffmans, R., & Basler, K. (2006) · Current Biology · doi:10.1016/j.cub.2006.04.019 · Cited by 200 · see citing works
Activation domains of stably bound GAL4 derivatives alleviate repression of promoters by nucleosomes
Workman, J. L., Taylor, I. C. A., & Kingston, R. E. (1991) · Cell · doi:10.1016/0092-8674(91)90237-s · Cited by 224 · see citing works
Mediator protein mutations that selectively abolish activated transcription
Myers, L. C., Gustafsson, C. M., Hayashibara, K. C., Brown, P. O., & Kornberg, R. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.67 · Cited by 181 · see citing works
Self-citationMediator subunit MED25 links the jasmonate receptor to transcriptionally active chromatin
An, C., Li, L., Zhai, Q., You, Y., Deng, L., Wu, F., Chen, R., Jiang, H., Wang, H., Chen, Q., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710885114 · Cited by 204 · see citing works
Mediator as a General Transcription Factor*
Takagi, Y., & Kornberg, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508253200 · Cited by 177 · see citing works
Self-citationHuman TAFII 105 is a cell type-specific TFIID subunit related to hTAFII130.
Dikstein, R., Zhou, S., & Tjian, R. (1996) · Cell · doi:10.1016/s0092-8674(00)81330-6 · Cited by 171
Abate, C., Luk, D., & Curran, T. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.7.3624-3632.1991 · Cited by 170
“In contrast, the N-terminal domain containing the proline-glycine region defined in this report as an in vitro activator domain also functions in vivo (6, 7, 26, 28).”
BackgroundInfluentialStructure of eukaryotic Mediator complexes.
Chadick, J. Z., & Asturias, F. (2005) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/j.tibs.2005.03.001 · Cited by 169 · see citing works
Yeast TAF IIS in a multisubunit complex required for activated transcription
Reese, J. C., Apone, L., Walker, S. S., Griffin, L. A., & Green, M. R. (1994) · Nature · doi:10.1038/371523a0 · Cited by 168 · see citing works
Mathur, S., Vyas, S., Kapoor, S., & Tyagi, A. K. (2011) · PLANT PHYSIOLOGY · doi:10.1104/pp.111.188300 · Cited by 181 · see citing works
Mediator-Dependent Recruitment of TFIIH Modules in Preinitiation Complex
Esnault, C., Ghavi-Helm, Y., Brun, S., Soutourina, J., van Berkum, N. L., Boschiero, C., Holstege, F. C. P., & Werner, M. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.06.021 · Cited by 172 · see citing works
Kimura, H., Tao, Y., Roeder, R. G., & Cook, P. R. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.8.5383 · Cited by 164 · see citing works
Davis, J. L., Kunisawa, R., & Thorner, J. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.4.1879-1892.1992 · Cited by 163 · see citing works
“Such a screen might uncover mutations in specific factors directly downstream of Stel2, possibly belonging to the newly proposed class of coactivator proteins (3, 42), as well as factors operating independently of Ste12 such as those affecting the general transcriptional machinery, chromatin structure, or other nontra…”
BackgroundAn Activator Binding Module of Yeast RNA Polymerase II Holoenzyme
Lee, Y. C., Park, J. M., Min, S., Han, S., & Kim, Y.-J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.2967 · Cited by 162 · see citing works
Wang, W.-D., Gralla, J., & Carey, M. F. (1992) · Genes & Development · doi:10.1101/gad.6.9.1716 · Cited by 154
Evidence for a mediator cycle at the initiation of transcription.
Svejstrup, J. Q., Li, Y. I., Fellows, J., Gnatt, A., Björklund, S., & Kornberg, R. (1997) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.94.12.6075 · Cited by 152 · see citing works
Self-citationTFIIF-TAF-RNA polymerase II connection.Preprint
Henry, N. L., Campbell, A., Feaver, W. J., Poon, D., Weil, P., & Kornberg, R. (1994) · Genes & Development · doi:10.1101/gad.8.23.2868 · Cited by 152 · see citing works
Self-citationStructural basis of eukaryotic gene transcription
Boeger, H., Bushnell, D. A., Davis, R., Griesenbeck, J., Lorch, Y., Strattan, J. S., Westover, K. D., & Kornberg, R. D. (2005) · FEBS Letters · doi:10.1016/j.febslet.2004.11.027 · Cited by 151 · see citing works
Self-citationMax, T., Søgaard, M., & Svejstrup, J. Q. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701345200 · Cited by 150 · see citing works
Transcriptional coactivators in yeast and beyond.
Guarente, L. P. (1995) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/s0968-0004(00)89120-3 · Cited by 149 · see citing works
Yeast and human TFIID with altered DNA-binding specificity for TATA elements.
Strubin, M., & Struhl, K. (1992) · Cell · doi:10.1016/0092-8674(92)90147-5 · Cited by 148
“…in the transcriptional activation mechanism, particularly regarding proposed interactions between TFIID and putative adaptor proteins (Berger et al., 1990; Kambadur et al., 1990; Kelleher et al., 1990; Lewin, 1990; Meisterernst et al., 1990; Peterson et al., 1990; Pugh and Tjian, 1990).”
BackgroundLong noncoding RNAs: new regulators in plant development.
Zhang, Y.-C., & Chen, Y.-Q. (2013) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2013.05.086 · Cited by 147 · see citing works
RNA polymerase II C-terminal repeat influences response to transcriptional enhancer signals
Scafe, C., Chao, D. M., Lopes, J. M., Hirsch, J., Henry, S., & Young, R. (1990) · Nature · doi:10.1038/347491a0 · Cited by 145 · see citing works
Goff, S. A., Cone, K. C., & Fromm, M. (1991) · Genes & Development · doi:10.1101/gad.5.2.298 · Cited by 139 · see citing works
Interactions between subunits of the Mediator complex with gene-specific transcription factors
Borggrefe, T., & Yue, X. (2011) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.07.022 · Cited by 132 · see citing works
Molecular analyses of metallothionein gene regulation.
Samson, S. L., & Gedamu, L. (1998) · Progress in Nucleic Acid Research and Molecular Biology · doi:10.1016/s0079-6603(08)61034-x · Cited by 139 · see citing works
Colgan, J., & Manley, J. (1992) · Genes & Development · doi:10.1101/gad.6.2.304 · Cited by 137 · see citing works
“Several classes of transcriptional activators appear to function through TFIID using a class of intermediary molecules known as coactivators or adaptors (Berger et al. 1990; Kelleher et al. 1990; Martin et al. 1990; Pugh and Tjian 1990), some of which have been partially purified (Dynlacht et al.”
BackgroundPositive and negative elements regulate a melanocyte-specific promoter
Lowings, P., Yavuzer, U., & Goding, C. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.8.3653-3662.1992 · Cited by 135
“be cell type specific, and it is entirely possible that a subset of such proteins mediates highly specific interactions between the basal initiation complex and upstream factors (15, 22, 28, 32, 33, 43, 49).”
BackgroundYeast SUB1 is a suppressor of TFIIB mutations and has homology to the human co‐activator PC4.
Knaus, R., Pollock, R., & Guarente, L. (1996) · EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00544.x · Cited by 124 · see citing works
Roles of TFIID in transcriptional initiation by RNA polymerase II.
Greenblatt, J. (1991) · Cell · doi:10.1016/0092-8674(91)90027-v · Cited by 122 · see citing works
Eukaryotic coactivators associated with the TATA box binding protein.
Gill, G., & Tjian, R. (1992) · Current Opinion in Genetics and Development · doi:10.1016/0960-9822(92)90538-l · Cited by 121
Association of the Mediator complex with enhancers of active genes
Kuras, L., Borggrefe, T., & Kornberg, R. (2003) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2036346100 · Cited by 120 · see citing works
Self-citationSelective Mediator dependence of cell-type-specifying transcription
Jaeger, M. G., Schwalb, B., Mackowiak, S. D., Velychko, T., Hanzl, A., Imrichová, H., Brand, M., Agerer, B., Chorn, S., Nabet, B., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0635-0 · Cited by 132 · see citing works
The RNA Polymerase II Elongation Complex
Shilatifard, A., Conaway, R. C., & Conaway, J. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161551 · Cited by 253 · see citing works
“The culmination of efforts by Kornberg and coworkers (2) to isolate a transcription factor referred to as Mediator ( 3 ), which was shown to be crucial for transcriptional activation by acidic activators, resulted in purification from yeast of a novel, high molecular mass form of RNA polymerase II composed of Mediator…”
BackgroundJones, R. D., Qian, Y., Siciliano, V., DiAndreth, B., Huh, J. H., Weiss, R., & Vecchio, D. D. (2020) · Nature Communications · doi:10.1038/s41467-020-19126-9 · Cited by 118 · see citing works
MED25 connects enhancer–promoter looping and MYC2-dependent activation of jasmonate signalling
Wang, H., Li, S.-Y., Li, Y., Xu, Y.-R., Wang, Y.-H., Zhang, R., Sun, W.-J., Chen, Q., Wang, X.-J., Li, C.-Y., et al. (2019) · Nature Plants · doi:10.1038/s41477-019-0441-9 · Cited by 115 · see citing works
The Mediator of RNA polymerase II
Blazek, E., Mittler, G., & Meisterernst, M. (2005) · Chromosoma · doi:10.1007/s00412-005-0329-5 · Cited by 107 · see citing works
Lobo, S., Lister, J., Sullivan, M. L., & Hernandez, N. (1991) · Genes & Development · doi:10.1101/gad.5.8.1477 · Cited by 114
Step, S. E., Lim, H., Marinis, J. M., Prokesch, A., Steger, D. J., You, S.-H., Won, K., & Lazar, M. A. (2014) · Genes & Development · doi:10.1101/gad.237628.114 · Cited by 97 · see citing works
“Support for this coactivator competition model, often referred to as squelching, has been largely based on TF overexpression experiments in transfection systems (Gill and Ptashne 1988; Kelleher et al. 1990; Kamei et al. 1996; Fronsdal et al. 1998; Lee et al. 2000; Li et al. 2000; Kim et al. 2001; Zhang and Teng 2001;…”
BackgroundMethodMediator Structural Conservation and Implications for the Regulation Mechanism
Cai, G., Imasaki, T., Takagi, Y., & Asturias, F. J. (2009) · Structure · doi:10.1016/j.str.2009.01.016 · Cited by 101 · see citing works
“Conserved structure and conformational changes in Mediator Following the discovery of Mediator in yeast (Flanagan et al., 1991; Kelleher et al., 1990), it was suggested that similar complexes might not be present or be as important in higher eukaryotic cells where the mechanism of transcription…”
BackgroundADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5, ADA2, or ADA3
Horiuchi, J., Silverman, N., Piña, B., Marcus, G., & Guarente, L. P. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3220 · Cited by 108 · see citing works
“In addition to these two types of factors, a third type whose members are referred to as mediators, coactivators, or adaptors has been isolated (3, 32, 44).”
BackgroundDuan, C., & Clemmons, D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.24844 · Cited by 108
Berkenstam, A. L., Vivanco, M. D., Barettino, D., Horikoshi, M., & Stunnenberg, H. G. (1992) · Cell · doi:10.1016/0092-8674(92)90443-g · Cited by 111 · see citing works
Activation of early gene expression in T lymphocytes by Oct-1 and an inducible protein, OAP40.
Ullman, K. S., Flanagan, W., Edwards, C., & Crabtree, G. (1991) · Science · doi:10.1126/science.1683003 · Cited by 108 · see citing works
Dominant negative mutations in yeast TFIID define a bipartite DNA-binding region.
Reddy, P., & Hahn, S. (1991) · Cell · doi:10.1016/0092-8674(91)90168-x · Cited by 107 · see citing works
Sze, J. Y., Woontner, M., Jaehning, J., & Kohlhaw, G. (1992) · Science · doi:10.1126/science.1439822 · Cited by 104 · see citing works
GAL4 disrupts a repressing nucleosome during activation of GAL1 transcription in vivo.Preprint
Axelrod, J., Reagan, M. S., & Majors, J. (1993) · Genes & Development · doi:10.1101/gad.7.5.857 · Cited by 102 · see citing works
ADA5/SPT20 links the ADA and SPT genes, which are involved in yeast transcription
Marcus, G., Horiuchi, J., Silverman, N., & Guarente, L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.6.3197 · Cited by 101 · see citing works
“These factors, termed coactivators or adapters, have been identified by using various genetic and biochemical methods and are thought to function by mediating the interaction between basal factors and activation domains (3, 31, 41).”
BackgroundDobrzański, P., Ryseck, R., & Bravo, R. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.3.1572-1582.1993 · Cited by 101 · see citing works
“This effect is likely to be mediated by cell-typespecific cofactors (7, 30, 46), which in the case of RelB might differentially interact with its N- and C-terminal domains.”
Background
- Authors
- Kelleher, R. J., Flanagan, P. M., & Kornberg, R. D.
- Affiliations
- Stanford Medicine (US)
- ORCID
- Kornberg, Roger D.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1990-06
- Volume
- 61
- Issue
- 7
- Pages
- 1209-1215
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2021893003
- Cited by
- 450
- References
- 35
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 3 · 2022: 5 · 2021: 13 · 2020: 20 · 2019: 12 · 2018: 14 · 2017: 10 · 2016: 8 · 2015: 8 · 2014: 10 · 2013: 16 · 2012: 8
- FWCI
- 20.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM-07365, GM-36859)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- RNA polymerase II, transcriptional activation, transcriptional coactivator, transcription factors
- MeSH terms
- beta-Galactosidase, Cell Nucleus, DNA-Binding Proteins, DNA, Fungal, Fungal Proteins, Kinetics, Phosphoproteins, Plasmids, Recombinant Fusion Proteins, RNA Polymerase II, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Trans-Activators, Gene Expression Regulation, Fungal, Simplexvirus, Saccharomyces cerevisiae Proteins
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