beyond the scope of this article, but details of one of the subunits is illustrative of the types of information that may be gathered for other subunits. regulation by Micro RNAs Micro RNAs are involved in regulating the expression of many proteins. Med1 is targeted by miR-1, which is important in gene regulation in cancers. The tumor suppressor miR-137 also regulates MED1. Mouse embryonic development Null mutants die at an early gestational age (embryonic day 11.5). By investigating hypomorphic mutants (which can survive 2 days longer), it was found that placental defects were primarily lethal and that there were also defects in cardiac and hepatic development, but many other organs were normal Mouse cells and tissues Conditional mutations can be produced in mice which affect only specific cells or tissues at specific times, so that the mouse can develop to adulthood and the adult phenotype can be studied. In one case, MED1 was found to participate in controlling the timing of events of meiosis in male mice. Conditional mutants in keratinocytes show differences in skin wound healing. A conditional mutant in mice was found to change dental epithelium into epidermal epithelium, which caused hair to grow associated with the incisors. Subunit composition The Mediator complex is composed at least 31 subunits in all eukaryotes studied: MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED28, MED29, MED30, MED31, CCNC, and CDK8. There are three fungal-specific components, referred to as Med2, Med3 and Med5. The subunits form at least three structurally distinct submodules. The head and the middle modules interact directly with RNA polymerase II, whereas the elongated tail module interacts with gene-specific regulatory proteins. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. The head module contains: MED6, MED8, MED11, SRB4/MED17, SRB5/MED18, ROX3/MED19, SRB2/MED20 and SRB6/MED22. The middle module contains: MED1, MED4, NUT1/MED5, MED7, CSE2/MED9, NUT2/MED10, SRB7/MED21 and SOH1/MED31. CSE2/MED9 interacts directly with MED4. The tail module contains: MED2, PGD1/MED3, RGR1/MED14, GAL11/MED15 and SIN4/MED16. The CDK8 module contains: MED12, MED13, CCNC and CDK8. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. In other species Below is a cross-species comparison of mediator complex subunits. Notes References Protein complexes Gene expression