Genome Disruption Impairs Key Developmental Genes

Removing cohesin protein complex disrupts 3D genome structure but surprisingly leaves most genes unaffected

Apr. 14, 2026 at 1:28am

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A highly textured, abstract painting in soft earth tones featuring sweeping geometric arcs, concentric circles, and precise botanical spirals, representing the complex three-dimensional structure of the genome and the vulnerability of key developmental genes when the cohesin protein is removed.A conceptual illustration of the genome's delicate three-dimensional structure and the disruption of critical developmental genes when the cohesin protein complex is disabled.NYC Today

Researchers at Weill Cornell Medicine found that temporarily disabling the cohesin protein complex, which organizes DNA into loops inside the cell nucleus, drastically disrupted the three-dimensional structure of the genome. However, most genes continued to function as usual, with the exception of a small group of developmentally important genes that failed to turn on properly without cohesin.

Why it matters

The study helps resolve a long-standing paradox in biology about genome architecture and cell function, which may provide insights into certain developmental disorders and cancers. Mutations in cohesin are commonly found in cancers and in disorders known as cohesinopathies that affect physical and cognitive development.

The details

The researchers studied mouse embryonic stem cells, which can develop into many different cell types. When they removed cohesin at the point when stem cells divide, the overall genomic structure was severely disrupted, with most DNA loops failing to re-form. However, most genes were largely unaffected, pointing to a resilient molecular memory that allows reactivation of the stem cell program even without normal DNA organization. But a small group of developmentally important genes, often sequestered in isolated areas of the genome, failed to turn on properly without cohesin, which is needed to bring them in contact with distant DNA elements that enhance their activity.

  • The study was published on April 13, 2026.

The players

Effie Apostolou

Associate professor of molecular biology in medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, and the senior author of the study.

UkJin Lee

Graduate student and Apostolou lab member, who performed the experiments and computational analysis for the study.

Weill Cornell Medicine

The institution where the research was conducted.

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What they’re saying

“We wanted to test this paradox under the most challenging conditions: right after cell division, when the entire genome architecture and gene expression program must be rebuilt from scratch.”

— Effie Apostolou, Associate professor of molecular biology in medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine

“This points to a resilient molecular memory that persists through cell division and allows reactivation of the stem cell program in the absence of this critical architectural protein.”

— UkJin Lee, Graduate student and Apostolou lab member

“The vulnerable genes tend to be developmentally important - such as those encoding transcription factors that direct cell identity. Therefore, the unique vulnerability of these genes to cohesin loss might have long lasting effects on proper development and differentiation.”

— Effie Apostolou, Associate professor of molecular biology in medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine

What’s next

Apostolou and her lab will continue to study what makes some genes dependent on cohesin, while others can function normally without it. They will also pursue genes vulnerable to cohesin loss and assess how even slight perturbations in their activity can lead to profound effects, including cancer or developmental impairment.

The takeaway

This study helps resolve a long-standing paradox in biology about genome architecture and cell function, suggesting that while the overall genomic structure is severely disrupted without the cohesin protein complex, a resilient molecular memory allows most genes to continue functioning. However, a small group of developmentally important genes are uniquely vulnerable to cohesin loss, which could have significant implications for understanding certain developmental disorders and cancers.