Distinct nuclear compartment-associated genome architecture in the developing mammalian brain

Area of Science:

• Neuroscience
• Genomics
• Epigenetics

Background:

• Nuclear compartments influence 3D genome organization and gene expression.
• The specific architecture of nuclear compartments in the mammalian brain remains largely unknown.

Purpose of the Study:

• To map genome interactions with nuclear lamina and speckles in developing mammalian brains.
• To investigate the role of nuclear compartments in brain development and disease.

Main Methods:

• Developed Genome Organization using CUT and RUN Technology (GO-CaRT) to map genomic interactions.
• Analyzed nuclear compartment-associated genome organization in developing mouse, macaque, and human brain regions.

Main Results:

• Nuclear lamina-associated domain (LAD) architecture in vivo differs from cultured cells and varies between dorsal and ventral neural precursors.
• Conserved LADs in human, macaque, and mouse brains are enriched for neural genes involved in synapse function.
• Speckle-associated domains are enriched for schizophrenia risk loci, suggesting a link between genetic variants and nuclear structures.

Conclusions:

• Nuclear compartments play a critical role in shaping genome organization in the developing brain.
• Distinct LAD architectures correlate with regional identity in the developing forebrain.
• Speckle-associated domains may physically interact with genetic risk factors for schizophrenia.