Enhancer grammar in development, evolution, and disease: dependencies and interplay

Each language has standard books describing that language's grammatical rules. Biologists have searched for similar, albeit more complex, principles relating enhancer sequence to gene expression. Here, we review the literature on enhancer grammar. We introduce dependency grammar, a model where enhancers encode information based on dependencies between enhancer features shaped by mechanistic, evolutionary, and biological constraints. Classifying enhancers based on the types of dependencies may identify unifying principles relating enhancer sequence to gene expression. Such rules would allow us to read the instructions for development within genomes and pinpoint causal enhancer variants underlying disease and evolutionary changes.

Automated summary

The text discusses how biologists study the grammatical rules related to enhancer sequences and gene expression by searching for principles governing their relationship, in order to decipher the instructions within genomes and identify potentially disease- and evolution-related enhancer variants.