Transcriptional repression in stochastic gene expression, patterning, and cell fate specification

Development is often driven by signaling and lineage-specific cues, yielding highly uniform and reproducible outcomes. Development also involves mechanisms that generate noise in gene expression and random patterns across tissues. Cells sometimes randomly choose between two or more cell fates in a mechanism called stochastic cell fate specification. This process diversifies cell types in otherwise homogenous tissues. Stochastic mechanisms have been extensively studied in prokaryotes where noisy gene activation plays a pivotal role in controlling cell fates. In eukaryotes, transcriptional repression stochastically limits gene expression to generate random patterns and specify cell fates. Here, we review our current understanding of repressive mechanisms that produce random patterns of gene expression and cell fates in flies, plants, mice, and humans. •Development involves mechanisms that generate noise in gene expression and random patterns across tissues.•Cells sometimes randomly choose between two or more cell fates to diversify cell types in otherwise homogenous tissues.•Repression stochastically limits expression to generate random patterns and specify cell fates in flies, mice, and humans.