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

Granton A Jindal¹, Emma K Farley¹

¹Division of Cardiology, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, La Jolla, CA 92093, USA.

Developmental Cell

|March 10, 2021

Summary

This summary is machine-generated.

Scientists propose a "dependency grammar" for enhancers, revealing how DNA sequences control gene expression. This framework could unlock developmental instructions and identify genetic variants linked to disease and evolution.

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Area of Science:

Genomics
Molecular Biology
Developmental Biology

Background:

Biological systems, like language, possess underlying rules governing their function.
Understanding the principles that dictate gene expression from enhancer sequences is a long-standing biological challenge.

Purpose of the Study:

To review the existing literature on enhancer grammar.
To introduce a novel model, dependency grammar, for understanding enhancer function.
To propose a classification system for enhancers based on dependency types.

Main Methods:

Literature review of enhancer grammar.
Development of the dependency grammar model.
Conceptual framework for classifying enhancers based on feature dependencies.

Main Results:

Enhancers encode information through dependencies between their features.
These dependencies are shaped by mechanistic, evolutionary, and biological constraints.
A classification system based on dependency types offers a potential unifying principle.

Conclusions:

Dependency grammar provides a framework for deciphering the relationship between enhancer sequence and gene expression.
This approach may enable reading developmental instructions encoded in genomes.
It could facilitate the identification of causal enhancer variants in disease and evolution.