Cited by 386Genomics and Chromatin DynamicsNuclear Structure and FunctionChromatin Remodeling and Cancer

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

A mediator required for activation of RNA polymerase II transcription in vitro

Flanagan, Peter M., Kelleher, Raymond J., Sayre, Michael H., Tschochner, Herbert, Kornberg, Roger D.·1991·Nature

Open this paper in CoChat — free account

Abstract

Activator proteins bind to enhancer DNA elements and stimulate the initiation of transcription. It has been proposed that activators contact general initiation factors at a promoter, and evidence for such direct interaction has been obtained. Studies of transcription in vitro, however, have suggested that activators might function through an intermediary molecule(s) distinct from the general factors. In the first of these studies, we exploited the finding that one activator could inhibit transcription stimulated by a second activator (activator interference or 'squelching'). This inhibition, which is attributed to competition between the activators for a common target factor, could not be relieved by addition of a large excess of general initiation factors, suggesting that the target for which activators compete is distinct from these factors. Similar conclusions came from the observation that TFIID's expressed from cloned genes fail to replace partially purified 'natural' TFIID fractions in supporting activation, evidently because they lacked some component present in the impure fractions. While these lines of evidence for a novel 'mediator' of activation were negative, we also showed that a partially purified fraction from yeast would reverse activator interference. This positive effect of a presumptive mediator provided an assay for its activity, but its role in activation was still only inferred. We now present direct evidence for a mediator which is required for stimulation of transcription in vitro by the activators GAL4-VP16 and GCN4, but which has no effect on transcription in the absence of activator protein.

Integrity signals

Registry

Crossref · 10.1038/350436a0

Cites

0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

A novel mediator between activator proteins and the RNA polymerase II transcription apparatus
Kelleher, R. J., Flanagan, P. M., & Kornberg, R. D. (1990) · Cell · doi:10.1016/0092-8674(90)90685-8 · Cited by 450
Self-citation

Show all 0 references

Research works printed but not linked: 26

Mitchell, P. J. & Tjian, R. Science 245, 371–378 (1989). · DOI
Struhl, K. Cell 49, 295–297 (1987). · DOI
Guarente, L. Cell 52, 303–305 (1988). · DOI
Sawadogo, M. & Roeder, R. G. Cell 43, 165–175 (1985). · DOI
Sawadogo, M. J. biol. Chem. 263, 11994–12001 (1988). · DOI
Horikoshi, M., Carey, M. F., Kakidani, H. & Roeder, R. G. Cell 54, 665–669 (1988). · DOI
Horikoshi, M., Hai, T., Lin, Y.-S., Green, M. R. & Roeder, R. G. Cell 54, 1033–1042 (1988). · DOI
Hai, T., Horikoshi, M., Roeder, R. G. & Green, M. R. Cell 54, 1043–1051 (1988). · DOI
Stringer, K. F., Ingles, C. J. & Greenblatt, J. Nature 345, 783–786 (1990). · DOI
Brandl, C. J. & Struhl, K. Proc. natn. Acad. Sci. U.S.A. 86, 2652–2656 (1989). · DOI
Kornberg, R. D. et al. in Gene Regulation and AIDS, (ed. Papas, T. S.) 9–18 (Gulf Publishing, Houston, 1989).
Triezenberg, S. J., Kingsbury, R. C. & McKnight, S. L. Genes Dev. 2, 718–729 (1988). · DOI
Gill, G. & Ptashne, M. Nature 334, 721–724 (1988). · DOI
Meyer, M.-E. et al. Cell 57, 433–442 (1989). · DOI
Hoey, T., Dynlacht, B. D., Peterson, M. G., Pugh, B. F. & Tjian, R. Cell 61, 1179–1186 (1990). · DOI
Pugh, B. F. & Tjian, R. Cell 61, 1187–1197 (1990). · DOI
Peterson, M. G., Tanese, N., Pugh, B. F. & Tjian, R. Science 248, 1625–1630 (1990). · DOI
Flanagan, P. M. et al. J. biol. Chem. 265, 11105–11107 (1990). · DOI
Ponticelli, A. S. & Struhl, K. Molec. cell. Biol. 10, 2832–2839 (1990). · DOI
Horikoshi, M., Yamamoto, T., Ohkuma, Y., Weil, P. A. & Roeder, R. G. Cell 61, 1171–1178 (1990). · DOI
Lue, N. F., Flanagan, P. M., Sugimoto, K. & Kornberg, R. D. Science 246, 661–664 (1989). · DOI
Chasman, D. I., Leatherwood, J., Carey, M., Ptashne, M. & Kornberg, R. D. Molec. cell. Biol. 9, 4746–4749 (1989). · DOI
Lue, N. F. & Kornberg, R. D. Proc. natn. Acad. Sci. U.S.A. 84, 8839–8843 (1987). · DOI
Schmidt, M. C., Kao, C. C., Pei, R. & Berk, A. J. Proc. natn. Acad. Sci. U.S.A. 86, 7785–7789 (1989). · DOI
Edwards, A. M. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2122–2126 (1990). · DOI
Hill, D. E., Hope, I. A., Macke, J. P. & Struhl, K. Science 234, 451–457 (1986). · DOI

Sorted by citations

Items 201–300 of 303

Mediator Subunits MED16, MED14, and MED2 Are Required for Activation of ABRE-Dependent Transcription in Arabidopsis
Lee, M., Dominguez-Ferreras, A., Kaliyadasa, E., Huang, W.-J., Antony, E., Stevenson, T., Lehmann, S., Schäfer, P., Knight, M., Ntoukakis, V., et al. (2021) · Frontiers in Plant Science · doi:10.3389/fpls.2021.649720 · Cited by 22
Preponderance of Free Mediator in the Yeast Saccharomyces cerevisiae*
Takagi, Y., Chadick, J. Z., Davis, J. A., & Asturias, F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500150200 · Cited by 22
Identification of a coactivator that increases activation of transcription by serum response factor and GAL4-VP16 in vitro.
Zhu, H.-X., & Pyrwes, R. (1992) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.89.12.5291 · Cited by 22
Genome-wide CRISPR screens reveal cyclin C as synthetic survival target of BRCA2
Tang, M., Pei, G., Su, D., Wang, C., Feng, X., Srivastava, M., Chen, Z., Zhao, Z., & Chen, J. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab540 · Cited by 22
Calcineurin Broadly Regulates the Initiation of Skeletal Muscle-Specific Gene Expression by Binding Target Promoters and Facilitating the Interaction of the SWI/SNF Chromatin Remodeling Enzyme
Witwicka, H., Nogami, J., Syed, S. A., Maehara, K., Padilla-Benavides, T., Ohkawa, Y., & Imbalzano, A. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00063-19 · Cited by 21
“Dephosphorylated NFAT translocates to the 67 nucleus and binds to promoter regions of target genes to regulate gene expression (28-31).”
Background
The Structural Basis of Transcription: 10 Years After the Nobel Prize in Chemistry
Hantsche-Grininger, M., & Cramer, P. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201608066 · Cited by 31
Functional and physical interactions within the middle domain of the yeast mediator
Hallberg, M., Hu, G.-Z., Tronnersjö, S., Shaikhibrahim, Z., Balčiūnas, D., Björklund, S., & Ronne, H. (2006) · Zeitschrift für Induktive Abstammungs- und Vererbungslehre · doi:10.1007/s00438-006-0135-7 · Cited by 21
“M. Hallberg · Z. Shaikhibrahim · S. Björklund Department of Medical Biochemistry and Biophysics, Umeå University, 0187 Umeå, Sweden G. Z. Hu · S. Tronnersjö · D. Balciunas · H. Ronne (&) Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, 75123 Uppsala, Sweden e-mail: Hans.Ronne@imbim.uu.…”
BackgroundInfluential
A novel chimeric promoter that is highly responsive to hypoxia and metals
Lee, J.-Y., Lee, Y.-S., Kim, J.-M., Kim, K., Lee, J.-S., Jang, H.-S., Shin, I.-S., Suh, W., Jeon, E.-S., Byun, J., et al. (2006) · Gene Therapy · doi:10.1038/sj.gt.3302728 · Cited by 21
The RNA polymerase II carboxy-terminal domain: links to a bigger and better 'holoenzyme'?
Emili, A., & Ingles, C. (1995) · Current Opinion in Genetics and Development · doi:10.1016/0959-437x(95)80009-3 · Cited by 21
Transcriptional activation in vitro by the human immunodeficiency virus type 1 Tat protein: evidence for specific interaction with a coactivator(s).
Song, C.-Z., Loewenstein, P., & Green, M. (1994) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.91.20.9357 · Cited by 21
The mediator complex.
Björklund, S., & Gustafsson, C. (2004) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(04)67002-1 · Cited by 21
Super enhancers as master gene regulators in the pathogenesis of hematologic malignancies
Debek, S. M., & Juszczyński, P. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188697 · Cited by 23
Saccharomyces cerevisiae: A Unicellular Model Genetic Organism of Enduring Importance
Hanson, P. K. (2018) · Current Protocols Essential Laboratory Techniques · doi:10.1002/cpet.21 · Cited by 23
Regulation of metabolism by the Mediator complex
Youn, D. Y., Xiaoli, A. M., Pessin, J. E., & Yang, F. (2016) · Biophysics Reports · doi:10.1007/s41048-016-0031-6 · Cited by 20
“Keywords Transcription, Mediator, Cofactor, Metabolism, Insulin resistance, Obesity”
Background
Establishment of cell fate during early Drosophila embryogenesis requires transcriptional Mediator subunit dMED31.
Bosveld, F., van Hoek, S., & Sibon, O. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2007.11.019 · Cited by 19
“, 2005) which was first identified in budding yeast (Flanagan et al., 1991) and consists of four large modules; head, middle, tail and an Srb8–11 module (Asturias et al.”
Background
Transcriptional interference caused by GCN4 overexpression reveals multiple interactions mediating transcriptional activation
Tavernarakis, N., & Thireos, G. (1995) · Molecular and General Genetics MGG · doi:10.1007/bf00290348 · Cited by 19
Insights into the regulatory role and clinical relevance of mediator subunit, MED12, in human diseases
Srivastava, S., & Kulshreshtha, R. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30099 · Cited by 18
“They were discovered in yeast as modulators of activator dependent transcription and were defined as a prerequisite for transcription of nearly all protein‐ coding genes (Flanagan et al., 1991).”
Background
Specific Defects in Different Transcription Complexes Compensate for the Requirement of the Negative Cofactor 2 Repressor in Saccharomyces cerevisiae
Peiró-Chova, L., & Estruch, F. (2007) · Genetics · doi:10.1534/genetics.106.066829 · Cited by 18
“E-mail: francisco.estruch@uv.es Genetics 176: 125–138 (May 2007) complex known as mediator.”
Background
The Schizosaccharomyces pombe genes sep10 and sep11 encode putative general transcriptional regulators involved in multiple cellular processes
Szilágyi, Z., Grallert, Á., Németh, N., & Sipiczki, M. (2002) · Zeitschrift für Induktive Abstammungs- und Vererbungslehre · doi:10.1007/s00438-002-0773-3 · Cited by 18
“cerevisiae as an intermediary complex of proteins that mediates signal transfer between gene-specific transcriptional activators and the basal transcription machinery (Flanagan et al. 1991).”
Background
Interspersion of an unusual GCN4 activation site with a complex transcriptional repression site in Ty2 elements of Saccharomyces cerevisiae
Türkel, S., & Farabaugh, P. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.4.2091-2103.1993 · Cited by 18
“more transcriptional coactivators, as do several activators (16, 24, 75).”
Background
Not the same thing: metastatic PTCs have a different background than ATCs
de Biase, D., Torricelli, F., Ragazzi, M., Donati, B., Kuhn, E., Visani, M., Acquaviva, G., Pession, A., Tallini, G., Piana, S., et al. (2018) · Endocrine Connections · doi:10.1530/ec-18-0386 · Cited by 20
Biochemical and redox characterization of the mediator complex and its associated transcription factor GeBPL, a GLABROUS1 enhancer binding protein
Shaikhali, J., Davoine, C., Brännström, K., Rouhier, N., Bygdell, J., Björklund, S., & Wingsle, G. (2015) · Biochemical Journal · doi:10.1042/bj20150132 · Cited by 21
Control of gene transcription by Mediator in chromatin.
Ries, D., & Meisterernst, M. (2011) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.08.004 · Cited by 17
“A Mediator activity as then described in yeast extracts [3].”
Method
Introduction to the Thematic Minireview Series: Chromatin and transcription
Gottesfeld, J., & Carey, M. F. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm118.004544 · Cited by 16
“Mediator was first discovered by Kornberg and colleagues (8) and shown to be essential for activated transcription in vitro.”
Background
Cyclin C regulates adipogenesis by stimulating transcriptional activity of CCAAT/enhancer-binding protein α
Song, Z., Xiaoli, A. M., Zhang, Q., Zhang, Y., Yang, E. S. T., Wang, S., Chang, R. R., Zhang, Z. D., Yang, G., Strich, R., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.776229 · Cited by 17
Respiratory Syncytial virus NS1 protein targets the transactivator binding domain of MED25
Dong, J.-Q., Basse, V., Bierre, M., de Oliveira, A. P., Vidalain, P.-O., Sibille, P., Tangy, F., Galloux, M., Éléouët, J., Sizun, C., et al. (2021) · bioRxiv · doi:10.1101/2021.11.19.469356 · Cited by 14
SWI/SNF complexes and facilitation of TATA binding protein:nucleosome interactions.
Imbalzano, A. (1998) · Methods · doi:10.1006/meth.1998.0634 · Cited by 14
Plant Biosynthetic Engineering Through Transcription Regulation: An Insight into Molecular Mechanisms During Environmental Stress
Srivastava, R., Mohan, K., & Srivastava, R. (2017) · Energy, environment, and sustainability · doi:10.1007/978-981-10-7434-9_4 · Cited by 20
The Mediator complex and the role of protein-protein interactions in the gene regulation machinery
Sierecki, E. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.08.006 · Cited by 17
Tissue specific expression profile of Mediator genes in Arabidopsis
Pasrija, R., & Thakur, J. (2013) · Plant Signalling & Behavior · doi:10.4161/psb.23983 · Cited by 13
“Later on, Mediator was purified and characterized to be a gigantic multiprotein complex required by RNA polymerase II for the transcription of its target genes.(3-5) It was found to play important role in facilitating the assembly of the preinitiation complex.”
Molecular genetic analysis of a prokaryotic transcriptional coactivator: functional domains of the bacteriophage T4 gene 33 protein
Winkelman, J. W., Kassavetis, G., & Geiduschek, E. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.4.1164-1171.1994 · Cited by 13
“Although the concept of the coactivator was developed to rationalize certain in vitro experiments on transcriptional initiation by eukaryotic RNA polymerase 11 (4, 7, 21, 24, 31), the prokaryotic gp33 was the first transcriptional activator to be molecularly and functionally characterized (13).”
Background
OsMED25‐OsWRKY78 Mediated Transcriptional Activation of OsGA20ox1 Positively Regulates Plant Height in Rice
Miao, Y., Xu, C.-X., Zhang, Y., Zhou, H.-P., & Xu, Q. (2025) · Plant, Cell and Environment · doi:10.1111/pce.15441 · Cited by 12
“Mediators were first found in yeast (Flanagan et al. 1991).”
Molecular and Phylogenetic Analyses of the Mediator Subunit Genes in Solanum lycopersicum
Wang, Y., Liang, H., Chen, G., Liao, C., Wang, Y., Hu, Z., & Xie, Q. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01222 · Cited by 14
The MED30 subunit of mediator complex is essential for early plant development and promotes flowering in Arabidopsis thaliana
Jaskolowski, A., Iñigo, S., Arellano, S. M., Arias, L. A., Fiol, D., Sede, A., Oldra, M. B., Lorenzi, H., Muschietti, J., Pagnussat, G., et al. (2019) · Development · doi:10.1242/dev.175224 · Cited by 12
“It was first discovered in yeast as an essential component for activation of in vitro transcription (Flanagan et al., 1991; Kelleher et al., 1990), and was subsequently purified from human cells (Fondell et al.”
Background
Toward understanding of the mechanisms of Mediator functionin vivo: Focus on the preinitiation complex assembly
Eychenne, T., Werner, M., & Soutourina, J. (2017) · Transcription · doi:10.1080/21541264.2017.1329000 · Cited by 19
“The discovery of Mediator originates from the observation of the activator interference phenomenon attributed to a competition between two activators for a common intermediate factor in yeast RNA polymerase II (Pol II) transcription in vitro.(1,2) These studies provided the first evidence for the existence of a Mediat…”
Background
The yeast mediator.
Björklund, S., Buzaitė, O., & Hallberg, M. (2001) · Molecules and Cells · doi:10.1016/s1016-8478(23)17015-4 · Cited by 12
How do eukaryotic activator proteins stimulate the rate of transcription by RNA polymerase II?
Ham, J., Steger, G., & Yaniv, M. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)80906-w · Cited by 12
Chromatin-remodeling complexes involved in gene activation by the glucocorticoid receptor
Wallberg, A. E., Wright, A. P. H., & Gustafsson, J.-Α. (2000) · Vitamins and hormones · doi:10.1016/s0083-6729(00)60017-1 · Cited by 12
Coping with Drought and Salinity Stresses: Role of Transcription Factors in Crop Improvement
Ribichich, K. F., Arce, A. L., & Chan, R. L. (2013) · Wiley eBooks · doi:10.1002/9783527675265.ch24 · Cited by 9
Yeast GAL11 protein stimulates basal transcription in a gene‐specific manner by a mechanism distinct from that by DNA‐bound activators
Sakurai, H., Ohishi, T., Amakasu, H., & Fukasawa, T. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)80098-7 · Cited by 11
Suppression of p53 response by targeting p53-Mediator binding with a stapled peptidePreprint
Allen, B., Quach, K., Jones, T., Levandowski, C. B., Ebmeier, C. C., Rubin, J. D., Read, T. J., Dowell, R. D., Schepartz, A., & Taatjes, D. (2019) · bioRxiv · doi:10.1101/757401 · Cited by 10
“cerevisiae using an in vitro assay to screen for factors required for TF-dependent transcription (Flanagan et al. 1991); similar functions have been confirmed for mammalian Mediator complexes (Fondell et al.”
Background
Identification of Mdmed Family, Key Role of Mdmed81, and Salicylic Acid at the Right Time of Year Triggers Mdmed81 to Induce Flowering in Malus Domestica
Shah, K., An, N., Cheng, B., Qi, S.-Y., Moale, C., Kamanova, S., Han, M., Ren, X.-L., & Xing, L. (2022) · Social Science Research Network · doi:10.2139/ssrn.4059156 · Cited by 9
Transcriptional regulators of seven yeast species: Comparative genome analysis — Review
Drobná, E., Bialková, A., & Šubík, J. (2008) · Folia Microbiologica · doi:10.1007/s12223-008-0044-8 · Cited by 9
RhMED15a-like, a subunit of the Mediator complex, is involved in the drought stress response in Rosa hybrida
Xie, N., Shi, H., Shang, X., Zhao, Z., Fang, Y. M., Wu, H., Luo, P., Cui, Y., & Chen, W. (2024) · BMC Plant Biology · doi:10.1186/s12870-024-05059-8 · Cited by 9
“Initially discovered in yeast, Mediator has proven to be essential for in vitro transcription activation [14, 15].”
Recent progress in structural biology: lessons from our research history
Nitta, R., Imasaki, T., & Nitta, E. (2018) · Microscopy · doi:10.1093/jmicro/dfy022 · Cited by 10
Control of Muscle Metabolism by the Mediator ComplexPreprint
Amoasii, L., Olson, E. N., & Bassel‐Duby, R. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029843 · Cited by 8
“First discovered in yeast as an essential regulator of activator-induced transcription, the Mediator complex has subsequently been isolated from mammalian cells in active and inactive forms (Flanagan et al. 1991).”
Background
ScMED7, a sugarcane mediator subunit gene, acts as a regulator of plant immunity and is responsive to diverse stress and hormone treatments
Zhang, X., Yang, Y., Zou, J., Chen, Y., Wu, Q., Guo, J., Que, Y., & Xu, L. (2017) · Molecular Genetics and Genomics · doi:10.1007/s00438-017-1352-y · Cited by 9
Biochemistry meets genetics in the holoenzyme.
Berk, A. J. (1995) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.92.26.11952 · Cited by 7
Positive and negative transcriptional regulation by the yeast GAL11 protein depends on the structure of the promoter and a combination of cis elements
Nishizawa, M., Taga, S., & Matsubara, A. (1994) · Molecular and General Genetics MGG · doi:10.1007/bf00290110 · Cited by 7
The Mediator Complex: A Regulatory Hub for Transcriptional Activity of Nuclear Receptors
Zhou, L., Zhao, M., Zhai, Y., & Lin, Q. (2025) · Cells · doi:10.3390/cells14171335 · Cited by 7
“The Mediator complex was first discovered by Dr. Roger Kornberg during his study on the gene transcription mechanism of Saccharomyces cerevisiae and was found to function in transcriptional activation [2,3].”
Temporal regulation of the Mediator complex during muscle proliferation, differentiation, regeneration, aging, and disease
Kolonay, D., Sattler, K. M., Strawser, C. N., Rafael-Fortney, J. A., Mihaylova, M., Miller, K. E., Lepper, C., & Baskin, K. K. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1331563 · Cited by 6
Comparative phylogenetic analysis of the mediator complex subunit in asparagus bean (Vigna unguiculata ssp. sesquipedialis) and its expression profile under cold stress
Liang, L., Wang, D., Xu, D., Xiao, J., Tang, W., Song, X., Yu, G., Liang, Z., Xie, M., Xu, Z., et al. (2024) · BMC Genomics · doi:10.1186/s12864-024-10060-4 · Cited by 6
“This component holds significant importance in the orchestration of eukaryotic gene expression [1].”
Background
Predicting bioprocess targets of chemical compounds through integration of chemical-genetic and genetic interaction networksPreprint
Simpkins, S. W., Nelson, J., Deshpande, R., Li, S. C., Piotrowski, J. S., Wilson, E. H., Gebre, A. A., Okamoto, R., Yoshimura, M., Costanzo, M., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/111252 · Cited by 7
“For example, 190 the top protein complex prediction for NPD1409 was “Kornberg’s mediator (SRB) complex,” 191 which plays an important role in the initiation of transcription as well as chromatin looping 192 [13,14].”
Background
Exploring the Role of Enhancer-Mediated Transcriptional Regulation in Precision Biology
Wang, X., Liu, D., Luo, J., Kong, D., & Zhang, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310843 · Cited by 7
An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cellsPreprint
Jones, R. D., Qian, Y., Siciliano, V., DiAndreth, B., Huh, J. H., Weiss, R., & Vecchio, D. D. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/867028 · Cited by 9
Global warming impact on rice crop productivity
Sengar, R., & Sengar, K. (2014) · doi:10.1201/b17684-14 · Cited by 4
Die molekularen Grundlagen der eukaryotischen Transkription (Nobel‐Vortrag)
Kornberg, R. (2007) · Angewandte Chemie · doi:10.1002/ange.200701832 · Cited by 4
Self-citation
Characterization of Mediator Complex and its Associated Proteins from Rice
Samanta, S., & Thakur, J. K. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7125-1_9 · Cited by 4
RNAPII: A Specific Target for the Cell Cycle Kinase Complex
Bakó, L., Nuotio, S., Dudits, D., Schell, J., & Koncz, C. (1994) · Results and problems in cell differentiation · doi:10.1007/978-3-540-48037-2_2 · Cited by 3
Differential regulation during development, aging, and disease implies heart cell specific functions of the Mediator Complex
Kolonay, D., Grueter, C. E., & Baskin, K. K. (2025) · Journal of Molecular and Cellular Cardiology Plus · doi:10.1016/j.jmccpl.2025.100456 · Cited by 3
“Protein components of Mediator are organized into four different regions-the head, middle, and tail submodules collectively comprise the core complex, and the kinase submodule, which can associate and disassociate with the core Mediator Complex [3,5,6].”
Cyclin-dependent kinases as mediators of aberrant transcription in prostate cancer
Rahman, R., & Selth, L. A. (2025) · Translational Oncology · doi:10.1016/j.tranon.2025.102378 · Cited by 5
Intergenic region between TATA-box binding protein and proteasome subunit C3 genes of Medaka function as the bidirectional promoter in vitro and in vivo.
Fujimori, K., Hazama, K., Kawasaki, T., Deguchi, T., & Yuba, S. (2012) · Gene · doi:10.1016/j.gene.2012.09.077 · Cited by 3
“(Flanagan et al., 1991; Kelleher et al., 1990; Kornberg, 2005, 2007).”
An autobiographic conversation with Roger D Kornberg on his work on transcription regulation
Kornberg, R. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402250 · Cited by 3
“In 1990 and 1991, Ray and Peter produced evidence for an additional factor required for this communication in a still crude yeast system.(17,18) This additional factor, which we referred to as Mediator, proved elusive.”
BackgroundSelf-citation
In vitro transcription of plant nuclear genes.
Schweizer, P. (1994) · Results and problems in cell differentiation · doi:10.1007/978-3-540-48037-2_5 · Cited by 3
Biallelic MED16 variants disrupt neural development and lead to an intellectual disability syndrome.
Huang, Y., Xiang, Z., Xiang, Y.-Q., Pan, H., He, M., Guo, Z.-M., Kanca, O., Liu, C., Zhang, Z., Zhan, H., et al. (2025) · Journal of genetics and genomics = Yi chuan xue bao · doi:10.1016/j.jgg.2025.04.004 · Cited by 2
The Contribution of Transcriptional Coregulators in the Maintenance of β-cell Function and Identity
Davidson, R. K., Kanojia, S., & Spaeth, J. M. (2020) · Endocrinology · doi:10.1210/endocr/bqaa213 · Cited by 5
Structure-function analysis of Arabidopsis TOPLESS reveals fundamental conservation of repression mechanisms across eukaryotesPreprint
Leydon, A. R., Wang, W., Gala, H. P., Gilmour, S., Juarez-Solis, S., Zahler, M. L., Zemke, J. E., Zheng, N., & Nemhauser, J. (2020) · bioRxiv · doi:10.1101/2020.03.04.976134 · Cited by 2
Strukturelle Grundlage der Transkription: 10 Jahre nach dem Chemie‐Nobelpreis
Hantsche-Grininger, M., & Cramer, P. (2016) · Angewandte Chemie · doi:10.1002/ange.201608066 · Cited by 2
The Role of Plant Mediator as a Gene Regulator to Tackle Climate Change: A Review
Wathugala, D. (2013) · doi:10.4038/jepsl.v1i1.5141 · Cited by 2
“Mediator is the evolutionary conserved multi-protein complex that binds RNA polymerase II and controls transcription of genes (Flanagan et al., 1991).”
Background
In the beginning there was RNA, then came transcription regulation: the Nobel Prize Lectures 2006
Melino, G., Nicotera, P., & Macino, G. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402259 · Cited by 2
RNA polymerase II: a "nobel" enzyme demystified.
Svejstrup, J. Q., Conaway, R., & Conaway, J. (2006) · Molecules and Cells · doi:10.1016/j.molcel.2006.11.016 · Cited by 2
The DNA target sequence influences the dependence of the yeast transcriptional activator Gcn4 on co-factors
Tavernarakis, N., & Thireos, G. (1997) · Molecular and General Genetics MGG · doi:10.1007/s004380050382 · Cited by 2
“…and Green 1993; Klein and Struhl 1994) and indirect interactions via proteins that serve as co-activators (Berger et al. 1990; Kelleher et al. 1990; Flanagan et al. 1991; Chiang et al. 1993, Kim et al. 1994, Lefstin et al. 1994) mediate ordered assembly of a productive transcription preinitiation…”
Background
Sequence requirements for embryonic transcriptional activation of a gastrula‐specific actin gene in Xenopus laevis
Brennan, S. (1991) · Molecular Reproduction and Development · doi:10.1002/mrd.1080300403 · Cited by 2
A Comprehensive Toolbox to Analyze Enhancer–Promoter Functions
Giaimo, B. D., Friedrich, T., & Borggrefe, T. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1597-3_1 · Cited by 3
Chromatin Structure with Respect to Histone Signature Changes during Cell Differentiation
Horáková, A. H., Bártová, E., & Kozubek, S. (2010) · Cell Structure and Function · doi:10.1247/csf.09021 · Cited by 4
“In Saccharomyces cervisiae, the “mediator complex” was first described as a factor necessary for activator-dependent stimulation of RNA polymerase II (Kelleher et al., 1990 and Flanagan et al., 1991).”
Background
Two prokaryotic transcriptional enhancer systems.
Ep, G. (1992) · doi:10.1016/s0079-6603(08)61046-6 · Cited by 2
A hypothetical model: Chromatin remodelers couple with acetyltransferases to trigger the elongation of RNA polymerase II (pol II)
Zhang, G. (2024) · Frontiers in Epigenetics and Epigenomics · doi:10.3389/freae.2024.1439973 · Cited by 8
“Upon binding of transcription factors (TFs) upstream of the transcription start site and downstream of nucleosomes at the −1 position (Gill and Ptashne, 1987), TFs recruit the Mediator (Flanagan et al., 1991; Thompson et al., 1993), which in turn recruits Pol II to the promoter region with the help of general transcri…”
Influential
SFR6 Protein of freezing tolerance in Arabidopsis does not affect localization of CBF1 protein
Wathugala, D., Knight, H., & Knight, M. (2015) · doi:10.4038/tare.v16i2.5274 · Cited by 1
MED16/SFR6 IS NECESSARY BUT NOT SUFFICIENT FOR COR GENE EX- PRESSION OF CBF PATHWAY
Wathugala, D., Knight, H., & Knight, M. (2013) · doi:10.4038/tare.v15i2.5241 · Cited by 1
A cold look at transcription.
Frank, J. (2002) · Structure · doi:10.1016/s0969-2126(02)00836-5 · Cited by 1
TAF2: A potential oncogene for hepatocellular carcinoma
Reghupaty, S. C. (2017) · doi:10.25772/pjkm-sv61 · Cited by 1
Roles of Mediator subunit CDK-8 in developmental and physiological responses in Caenorhabditis elegans
Grants, J. M. (2016) · doi:10.14288/1.0300224 · Cited by 1
Introduction to the Molecular Biology of the Cell
Marín-García, J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-404599-6.00001-9 · Cited by 20
The Dynamic Association of RNA Polymerase II with Initiation, Elongation, and RNA Processing Factors during the Transcription Cycle
Penheiter, K. L., & Jaehning, J. A. (2007) · Springer eBooks · doi:10.1007/978-0-387-40049-5_3 · Cited by 1
The autophagy protein Ambra1 regulates gene expression by supporting novel transcriptional complexes
Schoenherr, C., Byron, A., Griffith, B. G. C., Loftus, A. E. P., Wills, J. C., Munro, A. F., von Kriegsheim, A., & Frame, M. C. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.012565 · Cited by 18
A Transcription Factor-Centric View of Transcription Regulation
He, J., Chi, J., & Feng, S. (2026) · Biology · doi:10.3390/biology15100769
“Mediator subunits were identified as mutants affecting global transcription in yeast, and as protein subunits biochemically purified as complexes interacting with RNA pol II or TF activation domains [98,99].”
BmMed6 modulates mating behavior by ORs and antennae structural genes in the silkworm
Liying, Z., Dehong, Y., Longhao, T., Xiangyi, W., Kai, L., & Yongping, H. (2025) · iScience · doi:10.1016/j.isci.2025.112017
The BET inhibitors JQ1, AZD5153, and I-BET151 co-opt ubiquitin proteasome system components for altering expression of the BRD4 interactome in a human B cell linePreprint
Nallur, G. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.09.566482
Distinct function of Mediator subunits in fungal development, stress response and secondary metabolism in fungal pathogen Fusarium verticillioidesPreprint
Zhou, Z., Yan, H.-J., Kim, M., & Shim, W. (2021) · bioRxiv · doi:10.1101/2021.02.11.430821
“Published studies indicated that the ‘core Mediator’ serves as a 75 bridge between DNA-binding transcription factors (TFs), Pol II as well as other components 76 in the transcription machinery, which collectively plays a crucial role in transcriptional 77 activation (7-10).”
Background
Structure of the Mammalian MediatorPreprint
Zhao, H., Young, N., Kalchschmidt, J. S., Lieberman, J., Khattabi, L. E., Casellas, R., & Asturias, F. (2020) · bioRxiv · doi:10.1101/2020.10.05.326918
A novel transcriptional signalling pathway mediated by the trafficking protein Ambra1 via scaffolding Atf2 complexes
Schoenherr, C., Byron, A., & Frame, M. (2020) · bioRxiv · doi:10.1101/2020.01.08.899328
“Amongst these were several components of the Mediator complex, a multiprotein complex functioning as a transcriptional coactivator for RNA Polymerase II (highlighted in red) (19,20).”
Background
Rôle du médiateur et des cohésines dans la réparation des dommages oxydatifs de l'ADN
Lebraud, E. (2018) · theses.fr (ABES) · doi:10.70675/a2b027cdza460z4df2zb7bcz644b30f238b5
“Composition et structure a. Structure globale du Médiateur Le Médiateur de la transcription fut découvert chez la levure dans les années 90 (Flanagan et al., 1991; Thompson et al., 1993).”
Background
Mediator and NER factors in transcription initiation
Bidon, B. (2017) · theses.fr (ABES) · doi:10.70675/12739e56z4107z424czb63bz452d4c617054
“In the followings years, they initiate the identification of the MED composition and delineate its function(Flanagan et al., 1991; Kim et al., 1994).”
Background
Identification of the maize Mediator CDK8 module, and Dissociation insertional mutagenesis of ZmMed12aPreprint
Núñez-Rios, T., Ahern, K., Alonso-Nieves, A. L., Lepe-Soltero, D., Martinez-Camacho, C., García-Aguilar, M., Brutnell, T., Gillmor, C., & Sawers, R. J. H. (2016) · bioRxiv · doi:10.1101/097204
“One key regulator of transcription is Mediator, a multiprotein complex conserved from yeast to plants to animals, which was initially identified based on its requirement for transcription of virtually all protein-coding genes (Kelleher et al., 1990; Flanagan et al., 1991; Bourbon, 2008).”
Background
Investigating the role of the Mediator complex in plant defence
Fallath, T. (2016) · doi:10.14264/uql.2016.1067
Gene expression and differentiation
(2005) · Current Opinion in Genetics and Development · doi:10.1016/s0959-437x(05)80290-4
A comprehensive analysis of Med12 controlled (l)ncRNAs and characterization of a novel Sall1 antisense transcript
Pereira, T., & Filipe, B. (2020) · doi:10.17169/refubium-26726
“While the Young laboratory was studying extragenic suppressors of a pol II CTD mutation (Thompson et al. 1993), the Kornberg laboratory was identifying factors necessary for the response to activator proteins in a Pol II and GTFs reconstituted system (Flanagan et al. 1991).”
Method
Characterisation of the mediator complex in the malarial parasite Plasmodium falciparum
Iyer, U. B. (2018) · doi:10.32657/10356/73388
Transcriptional regulators of oxidative stress responses in the nematode Caenorhabditis elegans
Goh, Y. (2017) · doi:10.14288/1.0343459
“Originally discovered and purified in yeast as a factor that promotes activator-dependent gene transcription (Flanagan et al., 1991; Kim et al., 1994; Koleske and Young, 1994), Mediator mechanistically influences transcription, RNA polymerase II activity, and chromatin structure and function in numerous ways.”
Background
TRANSCRIPTIONAL REGULATION OF SPECIALIZED METABOLITES IN ARABIDOPSIS THALIANA AND CATHARANTHUS ROSEUS
Schluttenhofer, C. (2016) · doi:10.13023/etd.2016.451
“The multisubunit Mediator complex functions as both a coactivator and corepressor and recruits RNA polymerase II to the promoter of activated genes (Kelleher et al., 1990; Flanagan et al., 1991).”
Background

Authors: Flanagan, P. M., Kelleher, R. J., Sayre, M. H., Tschochner, H., & Kornberg, R. D.
Affiliations: Stanford Medicine (US)
ORCID: Tschochner, Herbert
Kornberg, Roger D.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1991-04
Volume: 350
Issue: 6317
Pages: 436-438
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/350436a0
OpenAlex: W2062439115
Cited by: 386
References: 0
Citations by year: 2026: 1 · 2025: 8 · 2024: 9 · 2023: 3 · 2022: 10 · 2021: 13 · 2020: 21 · 2019: 11 · 2018: 9 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 5 · 2013: 15 · 2012: 9
FWCI: 11.51
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: RNA polymerase II transcription, transcriptional activator, Mediator complex, TFIID, GAL4-VP16, GCN4, enhancers, transcriptional activation, yeast
MeSH terms: DNA-Binding Proteins, Enzyme Activation, Fungal Proteins, Nuclear Proteins, Recombinant Proteins, RNA Polymerase II, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Saccharomyces cerevisiae Proteins, Transcription Factor TFIID, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

A mediator required for activation of RNA polymerase II transcription in vitro

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Metadata

Record

About these checks