CUT homeobox factors modulate chromatin accessibility in neurons

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Neuronal identity is governed by complex transcriptional programs.
• The interplay between transcription factors and chromatin accessibility in neurons is not fully understood.
• CUT homeobox factors are present throughout the C. elegans nervous system.

Purpose of the Study:

• To investigate how CUT homeobox factors affect chromatin accessibility in neurons.
• To generate in vivo profiles of neuronal chromatin accessibility.
• To identify specific regulatory regions influenced by CUT factors.

Main Methods:

• Developed a method to isolate neuronal nuclei using fluorescence-activated sorting.
• Applied bulk ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) to profile chromatin accessibility.
• Compared chromatin accessibility in wild-type and CUT mutant C. elegans.

Main Results:

• Identified differences in chromatin accessibility within neuronal nuclei linked to CUT factors.
• Observed CUT-dependent accessibility changes primarily at promoter-proximal regions.
• Found these changes associated with genes involved in neuron-specific and pan-neuronal functions.

Conclusions:

• This study provides the first in vivo chromatin accessibility profiles for C. elegans neurons.
• CUT homeobox factors play a role in regulating chromatin accessibility at a subset of neuronal regulatory elements.
• These findings contribute to understanding the molecular mechanisms underlying neuronal gene regulation.