Review article: transcriptional events controlling the terminal differentiation of intestinal endocrine cells

Secretin-producing enteroendocrine cells arise from a multipotential endocr ine progenitor in the crypts of the small intestine. As these cells migrate up the crypt-villus axis, they produce secretin and stop dividing as they terminally differentiate and die. Transcription of the secretin gene is con trolled by a complex enhancer binding to multiple transcription factors. Th e basic helix-loop-helix protein, BETA2, binds to an E box sequence and ass ociates with the p300 coactivator to activate transcription of the secretin gene. Basic helix-loop-helix proteins appear to play a pivotal role in I-h e control of cellular differentiation. BETA2 induces cell cycle arrest and apoptosis in addition to activating secretin gene expression. Thus BETA2 ma y function as a master regulatory gene to coordinate terminal differentiati on of secretin cells.