Mapping Key Features of Transcriptional RegulatoryCircuitry in Embryonic Stem Cells

摘要

The process by which a single fertilized egg develops into a human being with more than 200 cell types—each with a distinctgene expression pattern controlling its cellular state—is poorly understood. Knowledge of the transcriptional regulatory cir-cuitry that establishes and maintains gene expression programs in mammalian cells is fundamental to understanding devel-opment and should provide the foundation for improved diagnosis and treatment of disease. Although it is not yet feasible tomap the entirety of this circuitry in vertebrate cells, recent work in embryonic stem (ES) cells has demonstrated that core fea-tures of the circuitry can be discovered through studies involving selected regulators. Here, we highlight the fundamentalinsights that have emerged from studies that examined the role of transcription factors, chromatin regulators, signaling path-ways, and noncoding RNAs in the regulatory circuitry of ES cells. Maps of regulatory circuitry and the insights that haveemerged from these studies have improved our understanding of global gene expression and are facilitating efforts to repro-gram cells for disease therapeutics and regenerative medicine.