Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression

Area of Science:

• Molecular Biology
• Genetics
• Chronobiology

Background:

• Mammalian circadian rhythm relies on clock gene feedback loops, influencing thousands of downstream genes.
• The impact of high-order chromosome structure on circadian gene expression remains largely unexplored.

Purpose of the Study:

• Investigate the role of chromatin structure proteins cohesin and CTCF in regulating circadian rhythm.
• Elucidate how chromosome architecture influences circadian gene expression patterns.

Main Methods:

• Utilized circular chromosome conformation capture sequencing (4C-seq) to examine Bmal1-bound super-enhancer interactions in mouse liver.
• Performed global analysis of cohesin and CTCF binding sites in relation to circadian oscillating genes.
• Conducted experiments in cohesin knockout cells.

Main Results:

• Circadian interacting loci and cohesin binding sites are largely stable throughout the circadian cycle.
• Cohesin-CTCF co-binding sites insulate circadian gene phases, while cohesin-non-CTCF sites enhance transcriptional rhythmicity.
• Cohesin is essential for driving circadian gene expression by promoting enhancer-promoter looping.

Conclusions:

• A model integrating cohesin and CTCF significantly enhances mechanistic understanding of circadian gene expression.
• This study reveals a novel connection between the circadian transcriptome and high-order chromosome structure.