Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

Area of Science:

• Neuroscience
• Genomics
• Epigenetics

Background:

• Neuronal gene expression is regulated by chromatin's 3D structure.
• Morphine's effects on neuronal gene networks are known, but its impact on 3D genome architecture is unclear.

Purpose of the Study:

• To investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons.
• To understand how morphine reshapes the spatial organization of the genome in neurons.

Main Methods:

• Digestion-ligation-only high-throughput chromosome conformation capture (DLO Hi-C) technology.
• Continuous morphine administration in rhesus monkeys for 90 days.
• RNA sequencing to identify differentially expressed genes.

Main Results:

• Morphine administration re-arranged chromosome territories and altered over half of topologically associated domains (TADs).
• Significant changes in differential looping events, including increased number and length.
• Differentially expressed genes were mapped to altered TAD boundaries and differential loops.

Conclusions:

• Morphine alters the 3D genomic architecture of cortical neurons.
• Changes in 3D genome organization correlate with altered gene networks associated with morphine effects.
• Findings provide insights into the connection between chromosome spatial organization and morphine-induced gene expression changes.