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Summary: Transcription factor binding to enhancer and promoter regions critical for homeostatic adult gene activation is established during development. To understand how cell-specific gene expression patterns are generated, we study the developmental timing of association of two prominent hepatic transcription factors with gene regulatory regions. Most individual binding events display extraordinarily high temporal variations during liver development. Early and persistent binding is necessary, but not sufficient, for gene activation. Stable gene expression patterns are the result of combinatorial activity of multiple transcription factors, which mark regulatory regions long before activation and promote progressive broadening of active chromatin domains. Both temporally stable and dynamic, short-lived binding events contribute to the developmental maturation of active promoter configurations. The results reveal a developmental bookmarking function of master regulators and illuminate remarkable parallels between the principles employed for gene activation during development, during evolution, and upon mitotic exit. : Karagianni et al. show that during liver development, master transcription factors bind to their targets in a temporally stable or dynamic manner. Transcription factors mark regulatory regions long before gene activation. Commonalities among the mechanisms of gene activation during development, evolution, and mitotic exit are described. Keywords: gene regulation, chromatin, development, liver, transcription factor, HNF4, CEBP