The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation

By S. Malik, R. Roeder. Nature reviews genetics, 2010

749 citations recorded by the source corpus.

The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/523cdc73c7c45d0e3875419ce481fe6609b651ed

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Citations in the corpus

Transcriptional Addiction in Cancer (2017, neutral): “The master TFs bind cooperatively to enhancer DNA elements and recruit coactivators and the transcription apparatus (Banerji et al., 1981; Benoist and Chambon, 1981; Bulger and Groudine, 2011; Gruss et al., 1981; Jolma et al., 2015; Lelli et al., 2012; Levine et al., 2014; Malik and Roeder, 2010; On”
The Human Transcription Factors. (2018, positive): “The Mediator complex, which bridges TFs and RNA polymerase II, is similarly associated with thousands of loci—possibly the majority of transcribed genes (Kagey et al., 2010)—and is recruited by dozens of TFs (Malik and Roeder, 2010).”
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes (2013, positive): “…transcription factors to recruit RNA Pol II to the promoters of target genes (Borggrefe and Yue, 2011; Conaway and Conaway, 2011; Kornberg, 2005; Malik and Roeder, 2010) and is essential for maintenance of ESC state and embryonic development (Ito et al., 2000; Kagey et al., 2010; Risley et al.,…”
Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers (2013, methodology): “…elements because enhancerbound transcription factors bind directly to Mediator (Borggrefe and Yue, 2011; Conaway and Conaway, 2011; Kornberg, 2005; Malik and Roeder, 2010; Taatjes, 2010) and because it has proven to produce high-quality evidence for enhancers in mammalian cells (Kagey et al.,…”
Transcription factors activate genes through the phase separation capacity of their activation domains (2018, background): “Anchored in place by the DBD, the AD interacts with coactivators, which integrate signals from multiple TFs to regulate transcriptional output (Allen and Taatjes, 2015; Juven-Gershon and Kadonaga, 2010; Malik and Roeder, 2010; Plaschka et al., 2016; Reiter et al., 2017; Soutourina, 2018; Taatjes, 20”
Transcriptional Regulation and its Misregulation in Disease (2013, positive): “…signaling pathways and other regulators during transcription initiation and during the switch to elongation (Berk, 2012; Borggrefe and Yue, 2011; Conaway and Conaway, 2011; Kagey et al., 2010; Kornberg, 2005; Lariviere et al., 2012; Malik and Roeder, 2010; Spaeth et al., 2011; Taatjes, 2010).”
Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA (2017, background): “Mediator is a protein complex which, along with cohesin, is involved in bridging together enhancers and promoters [73].”
Ever-changing landscapes: transcriptional enhancers in development and evolution (2016, background): “Coactivators are defined as factors that are ‘‘required for the function of DNA-binding activators, but not for basal transcription per se, and do not show site-specific binding by themselves’’ (Malik and Roeder, 2010).”
The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae (2012, background): “Studies on the response to heat and oxidative stress have provided important insight into nearly every aspect of eukaryotic cell biology, as we hope will be clear from our discussion.”
YY1 Is a Structural Regulator of Enhancer-Promoter Loops (2017, positive): “Mediator can physically bridge enhancer-bound transcription factors and the promoter-bound transcription apparatus (Allen and Taatjes, 2015; Jeronimo et al., 2016; Kagey et al., 2010; Malik and Roeder, 2010; Petrenko et al., 2016).”