Epigenomic landscapes during prefrontal cortex development and aging in rhesus

Area of Science:

• Neuroscience
• Epigenetics
• Developmental Biology

Background:

• The prefrontal cortex (PFC) is crucial for cognitive functions.
• Epigenetic mechanisms in PFC development and aging remain poorly understood.

Purpose of the Study:

• To profile epigenomic landscapes of rhesus monkey PFCs across developmental and aging stages.
• To elucidate the role of epigenetic dynamics in PFC development and aging.

Main Methods:

• Epigenomic profiling of rhesus monkey PFCs.
• Analysis of chromatin states, higher-order structure, interactions, and histone modifications.
• Identification of cis-regulatory elements and transcription factors.

Main Results:

• Coordinated epigenetic dynamics regulate stage-specific gene transcription during neurodevelopment, with significant changes around birth.
• Bivalent promoters pre-configure genes for neuronal differentiation and layer specification.
• A cis-regulatory module linked to basal radial glia development and primate brain size was identified, involving TFs like GLI3, CREB5, and SOX9.
• Schizophrenia-associated SNPs are enriched in super enhancers, highlighting their role in neural wiring.
• Loss of distal chromatin interaction and H3K27me3 signal characterize PFC aging, correlating with altered gene expression and transposon activation.

Conclusions:

• Epigenetic dynamics are central to primate prefrontal cortex development and aging.
• Specific epigenetic mechanisms are implicated in neurodevelopmental processes, brain evolution, and age-related changes.
• Super enhancers and aging-associated epigenetic alterations are relevant to neurological disorders and brain aging.