Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation
Yinan Li,
Jayson J. Smith,
Filipe Marques,
Anthony Osuma,
Hsin-Chiao Huang,
Paschalis Kratsios
Affiliations
Yinan Li
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA
Jayson J. Smith
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USA
Filipe Marques
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USA
Anthony Osuma
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA
Hsin-Chiao Huang
Committee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, IL 60637, USA
Paschalis Kratsios
Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA; Committee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USA; Corresponding author
Summary: AT-rich interaction domain 3 (ARID3) transcription factors are expressed in the nervous system, but their mechanisms of action are largely unknown. Here, we provide, in vivo, a genome-wide binding map for CFI-1, the sole C. elegans ARID3 ortholog. We identify 6,396 protein-coding genes as putative direct targets of CFI-1, most of which encode neuronal terminal differentiation markers. In head sensory neurons, CFI-1 directly activates multiple terminal differentiation genes, thereby acting as a terminal selector. In motor neurons, however, CFI-1 acts as a direct repressor, continuously antagonizing three transcriptional activators. By focusing on the glr-4/GRIK4 glutamate receptor locus, we identify proximal CFI-1 binding sites and histone methyltransferase activity as necessary for glr-4 repression. Rescue assays reveal functional redundancy between core and extended DNA-binding ARID domains and a strict requirement for REKLES, the ARID3 oligomerization domain. Altogether, this study uncovers cell-context-dependent mechanisms through which a single ARID3 protein controls the terminal differentiation of distinct neuron types.
