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. Author manuscript; available in PMC: 2011 Nov 16.
Published in final edited form as: Nat Rev Genet. 2010 Oct 13;11(11):761–772. doi: 10.1038/nrg2901

Figure 4. Modulation of Mediator function by ancillary factors: epigenetic silencing.

Figure 4

In concert with additional negatively acting factors, Mediator can contribute to long-term silencing of certain developmentally regulated loci. Starting with an active pre-initiation complex (PIC; which would likely contain the PC2 form of the Mediator), REST binding to the cognate site commits the gene to a heterochromatin fate as development proceeds. A ternary complex containing REST, the histone methyltransferase G9a and the intact Mediator is first assembled. The multipartite interactions are anchored through the MED12 subunit of the kinase module. Following G9a action and dimethylation of histone H3 lysine 9 (H3K9) to H3K9me2, heterochromatin protein 1 (HP1) and DNA methyltransferase 1 (DNMT1) are recruited to the site. Ultimately, the gene is embedded in transcriptionally inert heterochromatin marked by H3K9me2 and methylated DNA (CH3). Other factors (for example, histone deacetylase 1 and lysine-specific demethylase 1) that contribute to silencing are not shown. The figure is based on the findings described in REF. 57.