Mediator and Cohesin Connect Gene Expression and Chromatin Architecture

By M. Kagey, J. Newman, S. Bilodeau, Y. Zhan, David A. Orlando, Nynke L. van Berkum, Christopher C. Ebmeier, Jesse Goossens, P. Rahl, S. Levine and 3 more. Nature, 2010

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Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator–cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/84636bd34cde0cc035698e4505f9f5f235a7380f

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Citations in the corpus

Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites. (2013, neutral): “…and insulator markers (modified and variant histones, p300), three subunits of cohesin (SMC1A, SMC3, and RAD21), the cohesin loading factor NIPBL, twomediator subunits (MED1, MED12), and CTCF (Rollins et al., 1999; Heintzman et al., 2007; Visel et al., 2009; Kagey et al., 2010; Nasmyth, 2011).”
Transcriptional Addiction in Cancer (2017, positive): “Exemplifying this class of transcriptional signaling proteins are the components of the Mediator complex, which is recruited to enhancer-promoter regions by TFs in the context of transcription activation (Allen and Taatjes, 2015; Kagey et al., 2010).”
Control of Embryonic Stem Cell State (2011, background): “…are essential for ESC viability, including SetDB1 and the cohesin/condensin protein complexes (Dodge et al., 2004; Fazzio and Panning, 2010; Kagey et al., 2010), whereas others contribute to the stability of ESCs or establish a state that is essential for differentiation (Leeb et al.,…”
The Sox Family of Transcription Factors: Versatile Regulators of Stem and Progenitor Cell Fate (2013, neutral): “In contrast to this antagonistic relationship during development of the optic cup, Sox2 and Pax6 cooperate during lens development by forming a complex on lens-specific enhancer elements such as that of the delta crystalline gene (Kamachi et al., 2001).”
Super-enhancers in the control of cell identity and disease. (2013, positive): “The Mediator coactivator binds Nipbl, which loads cohesin, thus facilitating looping of enhancers to the promoters of their target genes (Kagey et al., 2010).”
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes (2014, positive): “…well-studied SMC complex that is loaded at enhancer-promoter loops, and can thus identify those interactions, and can also migrate to CTCF sites and thus identify those interactions as well (Kagey et al., 2010; Parelho et al., 2008; Rubio et al., 2008; Schaaf et al., 2013; Wendt et al., 2008).”
Transcriptional Regulation and its Misregulation in Disease (2013, positive): “For example, the ESC transcription factors Oct4 and Nanog bind to the P300 and Mediator coactivators (Chen et al., 2008; Kagey et al., 2010), which can then drive the formation of open chromatin and recruitment of the transcription apparatus.”
Transcriptional Amplification in Tumor Cells with Elevated c-Myc (2012, positive): “Furthermore, enhancers loop into proximity of core promoters at active genes (Bulger and Groudine, 2011; Göndör and Ohlsson, 2009; Kagey et al., 2010; Ong and Corces, 2011) and this proximity may facilitate binding of c-Myc to nearby enhancer elements once binding to sites in core promoters is satur”
Mapping nucleosome resolution chromosome folding in yeast by Micro-C (2015, positive): “…great interest, as Mediator recruitment of cohesin has previously been shown to play a role in chromosome folding in murine embryonic stem (ES) cells (Kagey et al., 2010; Phillips-Cremins et al., 2013), suggesting that chromosome domain compaction may be a conserved consequence of Mediator action.”
Activation of proto-oncogenes by disruption of chromosome neighborhoods (2015, background): “Transcriptional enhancers normally interact with their target genes through the formation of DNA loops (5-7), which typically are constrained within larger CTCF-cohesin mediated loops called insulated neighborhoods (8-10), which in turn can form clusters that contribute to topologically associating ”