esBAF and INO80C fine-tune subcompartments and differentially regulate enhancer-promoter interactions

Area of Science:

• * Molecular Biology
• * Genomics
• * Epigenetics

Background:

• * Genome organization relies on hierarchical chromatin structures, from nucleosomes to chromosome territories.
• * Nucleosome remodelers are crucial for DNA accessibility but their role in higher-order chromatin architecture is less understood.
• * esBAF and INO80C are key nucleosome remodelers involved in chromatin regulation.

Purpose of the Study:

• * To investigate the roles of esBAF and INO80C in 3D genome organization in mouse embryonic stem cells.
• * To determine how these remodelers affect chromatin topology at different scales.
• * To identify specific regulatory elements and genomic loci influenced by esBAF and INO80C.

Main Methods:

• * Hi-C experiments to analyze global and regional chromatin structures.
• * Promoter capture Micro-C (PCMC) to resolve promoter-anchored looping interactions at higher resolution.
• * Analysis of genomic loci enrichment for specific chromatin marks and transcription factors.

Main Results:

• * Loss of esBAF or INO80C minimally impacts global compartment and TAD structures.
• * Subcompartment organization is significantly altered upon loss of either remodeler, indicating effects on finer chromatin topology.
• * PCMC revealed altered promoter-anchored looping interactions, particularly at loci enriched for bivalent chromatin and key transcription factors (OCT4, SOX2, NANOG).

Conclusions:

• * esBAF and INO80C selectively regulate subcompartment identity and enhancer-promoter communication.
• * These remodelers play a critical role in organizing key regulatory loci in mouse embryonic stem cells.
• * Findings highlight an underappreciated role of nucleosome remodelers in higher-order chromatin organization.