DNA is the matter of inheritance, but how is its information decoded to develop an organism and to adapt to environmental changes? A process termed transcription is fundamental for reading out DNA. The so-called Mediator is a protein machine required for transcription. Mutations in Mediator genes cause certain diseases (e.g. cancers). To study Mediator components, we use worms and mice as models. We define how Mediator subunits ensure normal development and maintain balanced physiology by studying how their mutation causes specific developmental or metabolic defects. Defining these pathways may lead to diagnostic or therapeutic strategies for cancers or metabolic diseases.