Gene regulatory innovations from transposable elements in primate cerebellum development

Area of Science:

• Genomics
• Neuroscience
• Evolutionary Biology

Background:

• Transposable elements (TEs) are mobile DNA sequences implicated in genome evolution.
• Their role in cell-type-specific gene regulatory innovation, particularly in primate brain development, is not well understood.

Purpose of the Study:

• To investigate the contribution of TEs to cell-type-specific gene regulation in the primate cerebellum.
• To identify mechanisms of TE co-option into gene regulatory networks and their impact on evolution.

Main Methods:

• Single-cell multiomics data from human, macaque, marmoset, and mouse cerebella.
• A deep-learning model to predict cell-type-specific chromatin accessibility.
• Systematic assessment of TE co-option potential into gene regulatory networks.

Main Results:

• TE contributions vary across cell types due to constraints and preferential co-option.
• Twelve TE subfamilies with ancestral regulatory sequences were identified as having high co-option potential.
• Preservation of ancestral sequences and active chromatin environments determine TE accessibility.
• Lineage-specific accessible TEs contribute to human-specific gene expression.

Conclusions:

• Transposable elements are flexibly co-opted into cell-type-specific gene regulatory networks.
• TEs play a significant role in mammalian regulatory evolution and cell-type differentiation.
• A generalizable framework was introduced for analyzing TE contributions to regulatory evolution.