The  &lt;i&gt;C. elegans&lt;/i&gt; Regulatory Factor X (RFX) DAF-19M Module: A Shift From General Ciliogenesis to Ciliary and Behavioral Specialization

Ahn, Soungyub; Yang, Heeseung; Son, Sangwon; Park, Dongjun; Yim, Hyunsoo; Swoboda, Peter; Lee, Jun-Ho

doi:10.2139/ssrn.3915881

Cited by 1 publication

(1 citation statement)

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“…Because C. elegans animals lacking cfi-1 are viable (Shaham and Bargmann, 2002), these mutant strains provided a glance into the potential functions of ARID3 proteins during post-embryonic life. Candidate approaches that examined a handful of effector genes encoding neurotransmitter (NT) biosynthesis proteins and receptors suggested that CFI-1 acts as an activator of gene expression both in sensory neurons (IL2) and interneurons (AVD, PVC) (Shaham and Bargmann, 2002, Ahn et al, 2022. However, in ventral nerve cord motor neurons, CFI-1 is thought to act as a repressor of the glutamate receptor gene glr-4/GRIK1 (Kerk et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Control of neuronal terminal differentiation through cell context-dependent CFI-1/ARID3 functions

Smith

Marques

et al. 2022

Preprint

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ARID3 transcription factors are expressed in the nervous system, but their functions and mechanisms of action are largely unknown. Here, we generated in vivo a genome-wide binding map for CFI-1, the sole C. elegans ARID3 ortholog. We identified 6,396 protein-coding genes as putative direct targets of CFI-1, most of which (77%) are expressed in post-mitotic neurons and encode terminal differentiation markers (e.g., neurotransmitter receptors, ion channels, neuropeptides). To gain mechanistic insights, we focused on two neuron types. In sensory neurons (IL2 class), CFI-1 exerts a dual role: it acts directly to activate, and indirectly to repress, distinct terminal differentiation genes. In motor neurons, however, CFI-1 acts directly as a repressor, continuously antagonizing three transcriptional activators (UNC-3/Ebf, LIN-39/Hox4-5, MAB-5/Hox6-8). By focusing on a glutamate receptor gene (glr-4/GRIK1), we found CFI-1 exerts its repressive activity through proximal binding to the glr-4 locus. Further, the core DNA binding domain of CFI-1 is partially required for glr-4 repression in motor neurons. Altogether, this study uncovers cell context-dependent mechanisms through which a single ARID3 protein controls the terminal differentiation of distinct neuron types.

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