A dual enhancer-attenuator element ensures transient Cdx2 expression during mouse posterior body formation

Area of Science:

• Developmental Biology
• Gene Regulation
• Molecular Biology

Background:

• Cellular gene expression programs are crucial for assembling the vertebrate body plan.
• The transcription factor Cdx2 plays a critical role in trunk development, but its precise temporal regulation remains poorly understood.

Purpose of the Study:

• To elucidate the cis-regulatory mechanisms controlling the dynamic expression of Cdx2 in mouse caudal epiblast progenitors.
• To identify the elements responsible for the onset, maintenance, and termination of Cdx2 transcription.

Main Methods:

• CRISPR-mediated deletion of putative regulatory elements.
• In vitro cellular models.
• In vivo validation in mouse embryos.

Main Results:

• Distinct enhancers and a repressive element at the Cdx2 locus orchestrate its transient expression.
• A novel "attenuator" region, dependent on a nuclear receptor, was identified as critical for extinguishing Cdx2 expression.
• Modifying a single motif within the attenuator converted it into an enhancer, demonstrating its dual regulatory potential.

Conclusions:

• A dual cis-regulatory logic, involving sequential enhancers and a nuclear receptor-dependent attenuator, governs Cdx2 expression dynamics.
• This precise spatiotemporal control is essential for vertebrate body patterning.
• The findings provide new insights into the mechanisms of gene regulation during embryonic development.