Single-cell chromatin profiling reveals dynamic regulatory logic and enhancer elements in brain and retina...

Area of Science:

• Neuroscience
• Genomics
• Developmental Biology

Background:

• Cell type identity in the nervous system relies on cis-regulatory elements that control gene expression.
• Understanding how these regulatory programs change during post-embryonic neural development is crucial but poorly understood.

Purpose of the Study:

• To create a detailed, time-resolved atlas of chromatin accessibility in the zebrafish nervous system during development.
• To identify and characterize cell type-specific regulatory programs and their dynamic remodeling.
• To functionally validate candidate enhancers in vivo.

Main Methods:

• Generation of a single-cell chromatin accessibility atlas from approximately 95,000 zebrafish brain and retina nuclei across larval, juvenile, and adult stages.
• Integration of chromatin accessibility data with transcriptomic data.
• In vivo functional validation of candidate enhancers, including the slc1a3b locus.

Main Results:

• Definition of 212 discrete chromatin states and identification of widespread, cell type-specific chromatin reorganization during development.
• Linking motif accessibility to transcription factor expression, revealing maintained or reconfigured regulatory programs.
• Identification and functional validation of conserved enhancer modules driving gene expression, such as at the slc1a3b locus.

Conclusions:

• The study provides a systems-level framework for decoding neural regulatory logic during development.
• The generated atlas enables the functional dissection of conserved cis-regulatory programs in the vertebrate nervous system.
• This work enhances our understanding of how gene regulation shapes neural cell identity and function throughout life.