Functional signatures of evolutionarily young CTCF binding sites.

Area of Science:

• Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Novel CTCF binding sites in rodents arise from transposable element expansion, especially in the murine lineage.
• The precise mechanisms and functional consequences of these evolutionarily new CTCF binding sites remain largely unknown.
• This study focuses on novel subspecies-specific CTCF binding sites in Mus musculus domesticus and Mus musculus castaneus.

Purpose of the Study:

• To investigate the impact of novel subspecies-specific CTCF binding sites.
• To understand the evolutionary dynamics and functional significance of newly acquired CTCF binding sites.

Main Methods:

• Comparative genomics analysis of CTCF binding sites in two Mus subspecies.
• Assessment of binding site stability across tissues.
• Analysis of distances to regulatory elements and topologically associated domains (TADs).

Main Results:

• Transposable elements, specifically the B2-B4 family, independently drive CTCF binding site evolution in both lineages.
• A subset of young CTCF sites exhibit transcriptional functionality, demonstrated by stable binding across tissues.
• A novel BL6-specific immune locus with a 15-gene interferon cluster was identified, involving tandem duplication and CTCF regulation.

Conclusions:

• Thousands of CTCF binding sites acquire multiple functional signatures shortly after their integration into the genome.
• Transposable elements play a significant role in the rapid evolution and functionalization of CTCF binding sites.
• Novel CTCF binding sites can rapidly contribute to the formation of new regulatory architectures and immune loci.