Nanog, Oct4, and Sox2 form the core of a transcription factor network that 
maintains embryonic stem cells in the pluripotent state in both humans and mice. 
These critical factors have been implicated as both positive and negative 
regulators of transcription, varying by promoter and differentiation state of 
the cell. The Mediator complex, a ubiquitous conserved complex of approximately 
30 subunits, facilitates transcription by coordinating RNA polymerase II binding 
to target promoters via gene-specific activators and can be divided into several 
functional subcomplexes. Med12 is part of a subcomplex of four proteins 
associated with the core Mediator complex and has been found to function both in 
repressing and activating transcription when recruited to target promoters. We 
identified an interaction between Med12 and Nanog and present evidence of 
involvement of Med12 in regulation of Nanog function. Gene expression analysis 
of embryonic stem cells knocked down for Med12 showed a similarity to Nanog 
knockdown, with increased expression of Nanog-repressed targets and decreased 
expression of Nanog-activated targets. Using chromatin immunoprecipitation, we 
found that Med12 and Nanog co-occupied Nanog target promoters in embryonic stem 
cells and that Med12 dissociated from target promoters upon differentiation with 
kinetics similar to Nanog. Our results indicate that Nanog and Med12 function in 
concert to regulate Nanog target genes and identify a novel role for Med12 in 
embryonic stem cell regulation.