An intrinsic chromatin timer sets the tempo for development

Embryonic patterning depends on both spatially localized developmental determinants and temporal competence of the regulatory genome to respond. Classical misexpression experiments revealed restricted time windows of regulatory competence, but the underlying molecular mechanisms remain unknown. Using single molecule whole genome methods, we identify hundreds of cis-regulatory modules (CRMs) that undergo a transition in chromatin accessibility during early Drosophila development. A special subset of these CRMs is transiently active only during gastrulation. Their detailed cis-regulatory architectures convert small changes in the balance between two pioneer factors, Zelda and GAF, into sharp temporal thresholds of chromatin competence. Remarkably, these pulse CRMs open and close on schedule without key regulatory determinants such as Dorsal (fly NF-kB) and Twist and in the absence of transcription. This intrinsic chromatin timer triggers global changes in transcriptional dynamics as cells exit pluripotency.