New Study Finds Promoters and Enhancers Share Regulatory Logic

Researchers uncover surprising connections between two key gene-controlling DNA sequences

Published on Feb. 28, 2026

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Researchers at the Weill Institute for Cell and Molecular Biology have discovered that promoters and enhancers, two major types of gene-controlling DNA sequences, often perform the same functions and follow a shared regulatory logic. The findings, made possible through a new high-throughput assay called QUASARR-seq, could reshape how scientists design gene therapies, interpret disease-related mutations, and understand cancer genetics.

Why it matters

This research challenges the traditional view of promoters and enhancers as fundamentally distinct categories of gene regulators. The discovery that they can perform overlapping functions and influence each other provides a new framework for understanding gene expression and its role in health and disease. The insights could lead to more robust and predictable gene therapies, as well as better interpretation of disease-associated mutations in regulatory DNA.

The details

The study, led by graduate student Mauricio Paramo, used QUASARR-seq to measure the promoter and enhancer activities of thousands of human regulatory elements simultaneously. The researchers found that most promoters and enhancers can perform both functions, suggesting they follow a unified regulatory logic. They also discovered a two-way feedback loop, where enhancers activate promoters and promoters can boost nearby enhancers, creating high-activity "hubs" of transcription.

  • The study was published in Nature Communications on January 30, 2026.

The players

Haiyuan Yu

Tisch University Professor of Computational Biology at Cornell University's College of Agriculture and Life Sciences (CALS) and faculty at the Weill Institute.

Mauricio Paramo

A graduate student at the Weill Institute and the lead author of the study.

John Lis

Barbara McClintock Professor of Molecular Biology & Genetics at Cornell University, who collaborated with the research team.

Weill Institute for Cell and Molecular Biology

The research institution where the study was conducted.

Cornell University's College of Agriculture and Life Sciences (CALS)

The academic institution where Haiyuan Yu is a professor.

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What they’re saying

“What we're seeing is that promoters and enhancers draw from the same grammar. It's not just that they look similar - the same element can perform both functions. That's the key insight.”

— Mauricio Paramo, Graduate student at the Weill Institute (Nature Communications)

“Instead of a one-way street, we're seeing an all-by-all network of regulatory elements influencing each other. That gives us a new framework for understanding - and eventually engineering - gene expression.”

— Haiyuan Yu, Tisch University Professor of Computational Biology at Cornell University's CALS (Nature Communications)

The takeaway

This research proposes a more unified model of gene regulation, where promoters and enhancers operate through a shared regulatory code and can reinforce each other, rather than functioning as isolated switches. This new understanding could lead to more effective and predictable gene therapies, as well as better interpretation of disease-associated mutations in regulatory DNA.