Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation

• DOI: 10.1016/j.celrep.2023.112220
• Publication Date: 2023-03-09T20:12:15Z
• Authors: Yinan Li; Jayson J. Smith; Filipe Marques; Anthony Osuma; Hsin-Chiao Huang; Paschalis Kratsios
• Keywords: Motor Neurons; QH301-705.5; CP: Neuroscience; Animals; Cell Differentiation; Biology (General); Caenorhabditis elegans; Caenorhabditis elegans Proteins; Article; Transcription Factors

AT-rich interaction domain 3 (ARID3) transcription factors are expressed in the nervous system, but their mechanisms of action largely unknown. Here, we provide, vivo, a genome-wide binding map for CFI-1, sole C. elegans ARID3 ortholog. We identify 6,396 protein-coding genes as putative direct targets most which encode neuronal terminal differentiation markers. In head sensory neurons, CFI-1 directly activates multiple genes, thereby acting selector. motor however, acts repressor, continuously antagonizing three transcriptional activators. By focusing on glr-4/GRIK4 glutamate receptor locus, proximal sites and histone methyltransferase activity necessary glr-4 repression. Rescue assays reveal functional redundancy between core extended DNA-binding ARID domains strict requirement REKLES, oligomerization domain. Altogether, this study uncovers cell-context-dependent through single protein controls distinct neuron types.