Significance Whether animal neurons or plant cellular valves (called stomata), specialized cell-type differentiation is directed by the lineage-specific basic helix–loop–helix (bHLH) transcription factors that typically form heterodimers with ubiquitous bHLH proteins. How does a broadly expressed bHLH protein switch its lineage-specific heterodimeric partners? Here we identify a structural module, called the ACT-like domain, in the plant bHLH protein SCREAM. This domain plays a role in partner bHLH selectivity and is critical for the proliferation-to-differentiation switch within the cell lineages to make stomata, plant cellular valves for gas exchange and water control. Our work provides mechanistic insight into how plant transcription factors control cell-fate specification through an unanticipated heterodimeric partner selectivity interface.