The retinoblastoma tumor suppressor (RB) is best known for controlling cells’ decision to start replicating.

A new study shows that RB also plays an important role in organizing DNA inside the cell nucleus, a process that helps determine which genes are turned on or off.

The research was led by a team at Mass General Brigham Cancer Institute and Broad Institute of MIT and Harvard, including lead authors Hanjun Lee and Ioanna-Maria Gkotiakou, PhD, and senior authors Michael S. Lawrence, PhD, and Ioannis Sanidas, PhD.

Inside cells, DNA is folded into loops that bring genes into contact with regulatory elements controlling their expression. Cohesin is an important structural protein that helps form and maintain these loops.

The researchers found that RB normally helps prevent cohesin from building up at certain boundary regions in the genome. When RB is lost, cohesin accumulates, making boundaries more rigid and weakening key gene-regulating connections.

These changes mainly affect genes that help cells maintain their identity, adhere to their surroundings and move in controlled ways—functions essential for normal tissue development.

Overall, the findings reveal a previously underappreciated role for RB in shaping the three-dimensional structure of DNA, thereby supporting healthy gene activity and normal cell behavior. The insights also help explain why loss of RB is often linked to more aggressive cancers with disrupted gene regulation.

Published in Nature Communications on April 8, 2026 | Read the paper: “RB loss modulates chromatin organization by regulating cohesin dependent loops and enhancer promoter interactions”

Summary reviewed by: Ioannis Sanidas, PhD, senior author; Michael S. Lawrence, PhD, senior author