Choline Regulates SOX4 through miR-129-5p and Modifies H3K27me3 in the Developing Cortex

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Choline is crucial for neural progenitor cell (NPC) proliferation and differentiation in the developing cerebral cortex.
• The precise molecular mechanisms by which choline availability influences these processes remain incompletely understood.

Purpose of the Study:

• To elucidate the molecular pathway through which choline availability regulates NPCs in the developing brain.
• To identify key molecular players, including transcription factors and microRNAs, involved in choline-dependent neurogenesis.

Main Methods:

• Investigated the effect of choline availability on SOX4 protein levels in NPCs.
• Analyzed the role of microRNA-129-5p (miR-129-5p) in regulating SOX4 expression.
• Performed gain-of-function and loss-of-function assays for miR-129-5p.
• Assessed global H3K27me3 levels in the developing cortex.

Main Results:

• Low choline intake during neurogenesis reduces SOX4 protein levels in NPCs.
• This reduction is mediated by aberrant expression of miR-129-5p, not increased degradation.
• Decreased SOX4 and EZH2 (a downstream target) led to reduced H3K27me3, impacting NPC proliferation and differentiation.

Conclusions:

• Choline availability regulates the transcription factor SOX4 in NPCs through miR-129-5p.
• This nutrient-mediated pathway influences epigenetic modifications (H3K27me3) and critical developmental processes like cell proliferation and differentiation.
• Presents a novel mechanism for nutrient regulation of gene expression in brain development.