Overexpression of key ES cell transcription factors, including Sox2, Oct4, and Nanog, can reprogram many differentiated somatic cell types to a pluripotent state. Oct4, Sox2, and Nanog operate in large multiprotein complexes to positively regulate themselves and each other. Many aspects of the mechanism(s), however, are poorly understood. We have recently shown that loss of function of the transcription factor Bright/ARID3A efficiently promotes loss of differentiated phenotypes, spontaneous immortalization, and upregulation of known stem cells factors in somatic cells of mouse and man1. These reprogrammed cells demonstrate striking developmental plasticity in their ability to undergo induction to other differentitated cell types. Bright is the founding member of the ARID (AT-Rich Interacting Domain) family of transcription factors, whose members have been implicated in developmental fate decisions, cell cycle control, chromatin remodeling, and cell growth. Bright was first discovered as a component of a larger protein complex containing Bruton’s tyrosine kinase and TFII-I that up-regulates immunoglobulin heavy chain transcription. While Bright is expressed in multiple embryonic tissues, its expression is largely restricted to the earliest hematopoietic stem cell and B lineage cells in the adult where it is stringently regulated according to the B cell differentiation state. Chromatin immunoprecipitation and EMSA revealed that Bright binds directly to AT-rich motifs with the promoters of both Nanog and Oct4. These data along with the plastic phenotypes mediated by Bright loss of function suggest that Bright acts a direct repressor of at least some of the key transcriptional activators of pluripotency.