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A LINE-1 insertion upstream of FOXP2 promotes neuronal differentiation during primate evolution.

Jinhao Liu¹, Zihang Yin², Yonglin Peng³

¹Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, #800 Dongchuan Road, Biomedical Building#1-205, Shanghai, 200240, China.

|May 3, 2026

Summary

This summary is machine-generated.

Long interspersed element-1 (LINE-1) retrotransposons shaped the regulatory landscape of FOXP2, a gene crucial for language and cognition. This LINE-1 activity promoted primate-specific neuronal development and cortical neuron differentiation.

Keywords:

FOXP2 Enhancer LINE-1 Long-range chromatin interaction Neural stem cells Positive selection Primate

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Area of Science:

Evolutionary genomics
Neuroscience
Molecular biology

Background:

FOXP2 is vital for language and cognition, but its evolutionary path is unclear.
Long interspersed element-1 (LINE-1) retrotransposons influence genome regulation and development.
LINE-1's role in shaping FOXP2's regulatory elements is unknown.

Purpose of the Study:

Investigate the evolutionary role of LINE-1 in the FOXP2 regulatory landscape.
Understand how LINE-1 insertions impact FOXP2 function and primate brain evolution.

Main Methods:

Comparative evolutionary genomic analyses.
Integrative 3D genome mapping in human and marmoset neural stem cells.
Analysis of LINE-1 retrotransposition events.

Main Results:

Identified a 10.6 kb composite LINE-1 element (FOXP2-342L1) upstream of FOXP2, present in humans and chimpanzees.
FOXP2-342L1 mediates long-range chromatin interactions and shows signs of positive selection in humans.
This element acts as an evolutionary hub for LINE-1 insertions, regulating FOXP2 and promoting cortical neuron differentiation.

Conclusions:

LINE-1 retrotransposons reconfigured the 3D chromatin architecture of the FOXP2 regulatory landscape.
Discovered a primate-specific model of neuronal development influenced by LINE-1 activity during primate evolution.