The small GTPase RAB4 regulates endocytic recycling, a process that contributes to Major Histocompatibility Complex (MHC)-mediated antigen presentation by specialized antigen presenting cells (APC) of the immune system. The gene encoding the RAB4B isoform of RAB4 was singled out by two complementary genome-wide screens. One of these consisted of a computer scan to identify genes containing characteristic MHC class II-related regulatory sequences. The second was the use of chromatin immunoprecipitation coupled to microarrays (ChIP-on-chip) to identify novel targets of a transcriptional co-activator called the MHC class II transactivator (CIITA). We show that the RAB4B gene is regulated by a typical MHC class II-like enhancer that is controlled directly by both CIITA and the multiprotein transcription factor complex known as the MHC class II enhanceosome. RAB4B expression is thus activated by the same regulatory machinery that is known to be essential for the expression of MHC class II genes. This molecular link between the transcriptional activation of RAB4B and MHC class II genes implies that APC boost their antigen presentation capacity by increasing RAB4-mediated endocytic recycling.