Transcription-dependent dynamic supercoiling is a short-range genomic force

Area of Science:

• Molecular Biology
• Genomics
• Biophysics

Background:

• Transcription is known to influence DNA structure and nucleosome arrangement.
• These transcription-induced DNA modifications can provide feedback to the transcription machinery.
• Understanding the interplay between transcription and DNA dynamics is crucial for gene regulation.

Purpose of the Study:

• To investigate the relationship between active gene transcription and DNA topology.
• To map transcription-dependent dynamic supercoiling in human cells.
• To elucidate how different promoter outputs are managed in response to torsional stress.

Main Methods:

• Utilized psoralen photobinding to probe DNA topology in vivo within human Burkitt's lymphoma cells.
• Generated an ENCODE map of transcription-dependent dynamic supercoiling.
• Employed inhibitors of transcription and topoisomerases (I and II).
• Performed chromatin immunoprecipitation for RNA polymerase and topoisomerases I and II.

Main Results:

• Dynamic supercoils were observed to spread approximately 1.5 kilobases upstream of active gene start sites.
• Low-output promoters were adequately managed by topoisomerase I.
• High-output promoters additionally required topoisomerase II for managing torsional stress.
• Demonstrated genome-wide coupling between transcription and DNA topology.

Conclusions:

• Transcription-dependent dynamic supercoiling is a significant factor in gene regulation.
• The differential requirement for topoisomerases I and II highlights distinct mechanisms for managing torsional stress at low- and high-output promoters.
• The findings underscore the importance of DNA topology in the overall control of gene expression.