Eukaryotic gene transcription requires the concerted interplay of many factors. DNA-binding factors nucleate specific regulatory complexes on individual genes, culminating in assembly of functional RNA polymerase II (PolII). These complexes also contain transcriptional cofactors that serve various functions, such as chromatin remodeling and chromatin modification. Within this complex machinery, the sequence specific regulatory factors are generally thought to be the primary determinants that specify transcriptional output in response to a certain signal.
The Mediator is a conserved multi-protein coregulatory complex that, at the minimum, serves a critical linking function between regulatory factors and the transcription initiation machinery 
. Some Mediator subunits, such as yeast Med17 are required for essentially all PolII
-driven transcription 
. Similarly, in the nematode Caenorhabditis elegans
the subunit MDT-14/RGR-1 is broadly required for early embryonic transcription 
. However, in both organisms, some Mediator subunits are required only for expression of a restricted subset of all PolII
-transcribed genes 
. Indeed, many Mediator components influence specific physiological and/or developmental processes. For instance, mammalian MED1/TRAP220 is utilized by nuclear hormone receptors (NHRs) to implement programs such as adipogenesis (through peroxisome proliferators activated receptor γ (PPARγ) 
) and systemic detoxification (through the pregnane-X-receptor (PXR) and the constitutive androstane receptor (CAR) 
). Likewise, the C. elegans
Mediator subunits MDT-12/DPY-22, MDT-13/LET-19, and MDT-1.1/SOP-3 participate in vulva or male tail development 
. These studies raise the question of how individual components within the same regulatory complex can exert such separable effects. Also, it is unclear whether the specific functions of the coregulators are broader or narrower than those of the sequence specific regulatory factors with which they interact. Moreover, although certain Mediator subunits differentially affect related functions, the relationship between Mediator subunit utilization and a transcriptional mechanism or a physiological process is not known. Deciphering the mechanistic contributions of individual Mediator components to transcription is relevant in view of Mediator's conservation and its capacity to interact with numerous regulatory factors, thus influencing many biological processes 
In a previous study we found that the C. elegans
Mediator subunit MDT-15 integrates expression of certain metabolic genes in NHR-49-dependent and -independent ways 
. Others found that MDT-15 conveys regulation of fatty acid (FA) desaturases by the basic helix-loop-helix zipper protein SBP-1, the C. elegans
ortholog of the mammalian sterol regulatory element binding proteins (SREBPs) that regulate FA and cholesterol metabolism 
. Therefore, NHR-49 and SBP-1 appear to collaborate with MDT-15/MED15 to affect overlapping yet distinct sectors of metabolic genes. Hence, MDT-15 exhibits a broader spectrum of physiologic regulation than either individual regulatory factor, and could be viewed as an important node in a regulatory network that maintains metabolic homeostasis. Thus, analysis of individual Mediator components might reveal both upstream regulatory inputs and downstream regulatory mechanisms within a critical gene network.
To connect the function of MDT-15 in transcription to its precise physiologic role, we sought to more broadly define MDT-15's sphere of influence. As an initial step, we set out to globally discover new MDT-15-dependent genes in an unbiased fashion, and thus to identify previously unrecognized biological processes that lie downstream of MDT-15.