Gene Regulatory Interactions at Lamina-Associated Domains

Area of Science:

• Cell Biology
• Genomics
• Epigenetics

Background:

• The nuclear lamina creates a repressive chromatin environment at the cell nucleus periphery.
• Most genes in lamina-associated domains (LADs) are inactive, but some are expressed in local euchromatic regions.
• Regulation and enhancer interactions of these active genes in LADs remain unclear.

Purpose of the Study:

• To investigate the regulation and enhancer interactions of expressed genes within LADs.
• To explore the role of chromatin topology and nuclear lamina proteins in gene expression within LADs.

Main Methods:

• Integration of enhancer-capture Hi-C, chromatin state, and transcriptomic data.
• Fluorescence in situ hybridization (FISH) to analyze gene-enhancer proximity.
• Investigating the role of lamin A/C and lamin B1 in gene repression.

Main Results:

• Active genes in LADs form connections with enhancers both within and outside LADs.
• Gene-enhancer proximity changes during adipogenic differentiation.
• Lamin A/C, but not lamin B1, is involved in repressing genes at the border of active regions in LADs.

Conclusions:

• Chromatin topology at the nuclear lamina is compatible with gene expression.
• Spatial organization of chromatin supports dynamic gene regulation within the nuclear periphery.
• Specific lamin proteins play roles in regulating gene activity at the nuclear lamina.