JERUSALEM: Research released on Wednesday by Israeli and Scottish scientists sheds new light on how cells establish their specialized roles, with findings likely to transform regenerative medicine and cell therapy.
Researchers from Jerusalem’s Hebrew University and the University of Edinburgh uncovered how transcription factors (TFs), critical proteins responsible for regulating gene activity, navigate complex DNA and chromatin structures to define cellular identity. The findings were published in the peer-reviewed Nature journal.
Understanding how transcription factors navigate chromatin could enable scientists to bioengineer adult cells into other cell types.
For example, skin cells could potentially be reprogrammed into heart cells to treat an organ failure, or into insulin-producing beta cells to treat diabetes. The knowledge could also help identify chromatin-related gene regulation errors that cause developmental disorders, enabling early diagnosis and more targeted interventions.
“By uncovering how transcription factors interact with chromatin architecture, we can better understand gene regulation and cellular identity. This knowledge opens exciting possibilities for regenerative medicine, enabling us to precisely control cell fate and develop therapies for diseases caused by cellular dysfunction,” said Hebrew University’s Yosef Buganim, who led the research with Edinburgh University’s Abdenour Soufi.
Transcription factors bind to specific DNA sequences to regulate gene expression, directing cells to differentiate into specific types, such as skin, muscle, or placenta cells. While their ability to recognize DNA sequences is well-established, the exact mechanism behind their target selection within the vast genome has remained elusive. The study introduces a novel “guided search” mechanism, revealing how the 3D structure of DNA and chromatin acts as a roadmap for TFs.
By leveraging advanced technologies, the researchers explored how TF combinations influence distinct cell identities, focusing on embryo and placenta cells. They found that transcription factors dynamically cooperate or compete based on the chromatin landscape to target genes essential for cell type determination.
One key discovery was the influence of chromatin topology, which refers to the folding and looping of DNA within the nucleus. These structures guide TFs along DNA pathways or concentrate them at chromatin junctions densely packed with critical DNA motifs.
The findings also open new doors on enhancing gene-editing techniques such as CRISPR.
