Taxonomic distribution of proteins containing Med12 domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing Med12 domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Mediator modulates Gli3-dependent Sonic hedgehog signaling.

Zhou H, Kim S, Ishii S, Boyer TG
Mol Cell Biol. 2006; 26: 8667-82

The physiological and pathological manifestations of Sonic hedgehog (Shh)signaling arise from the specification of unique transcriptional programsdependent upon key nuclear effectors of the Ci/Gli family of transcriptionfactors. However, the underlying mechanism by which Gli proteins regulate target gene transcription in the nucleus remains poorly understood. Here, we identifyand characterize a physical and functional interaction between Gli3 and the MED12subunit within the RNA polymerase II transcriptional Mediator. We show that Gli3 binds to MED12 and intact Mediator both in vitro and in vivo through a Gli3transactivation domain (MBD; MED12/Mediator-binding domain) whose activityderives from concerted functional interactions with both Mediator and the histoneacetyltransferase CBP. Analysis of MBD truncation mutants revealed an excellentcorrelation between the in vivo activation strength of an MBD derivative and its ability to bind MED12 and intact Mediator in vitro, indicative of a criticalfunctional interaction between the Gli3 MBD and the MED12 interface in Mediator. Disruption of the Gli3-MED12 interaction through dominant-negative interferenceinhibited, while RNA interference-mediated MED12 depletion enhanced, both MBDtransactivation function and Gli3 target gene induction in response to Shhsignaling. We propose that activated Gli3 physically targets the MED12 interface within Mediator in order to functionally reverse Mediator-dependent suppressionof Shh target gene transcription. These findings thus link MED12 to themodulation of Gli3-dependent Shh signaling and further implicate Mediator in abroad range of developmental and pathological processes driven by Shh signaltransduction.

A unified nomenclature for protein subunits of mediator complexes linkingtranscriptional regulators to RNA polymerase II.

Bourbon HM, Aguilera A, Ansari AZ, Asturias FJ, Berk AJ, Bjorklund S, Blackwell TK, Borggrefe T, Carey M, Carlson M, Conaway JW, Conaway RC, Emmons SW, Fondell JD, Freedman LP, Fukasawa T, Gustafsson CM, Han M, He X, Herman PK, Hinnebusch AG, Holmberg S, Holstege FC, Jaehning JA, Kim YJ, Kuras L, Leutz A, Lis JT, Meisterernest M, Naar AM, Nasmyth K, Parvin JD, Ptashne M, Reinberg D, Ronne H, Sadowski I, Sakurai H, Sipiczki M, Sternberg PW, Stillman DJ, Strich R, Struhl K, Svejstrup JQ, Tuck S, Winston F, Roeder RG, Kornberg RD
Mol Cell. 2004; 14: 553-7