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During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
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Related Experiment Video

Updated: Aug 7, 2025

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

Yinan Li1, Jayson J Smith2, Filipe Marques2

  • 1Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.

Cell Reports
|March 10, 2023
PubMed
Summary
This summary is machine-generated.

The AT-rich interaction domain 3 (ARID3) transcription factor CFI-1 controls neuron development. This study reveals how CFI-1 activates or represses genes differently in sensory versus motor neurons.

Keywords:
ARID proteinsARID3C. elegansCFI-1CP: NeuroscienceCRISPR-Cas9 gene editingChIP-seqneuronal differentiationtranscription factors

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • AT-rich interaction domain 3 (ARID3) transcription factors are present in the nervous system.
  • Their precise roles and mechanisms in neuronal development remain largely uncharacterized.

Purpose of the Study:

  • To generate a genome-wide binding map for CFI-1, the C. elegans ARID3 ortholog.
  • To elucidate the cell-context-dependent mechanisms by which ARID3 controls neuronal terminal differentiation.

Main Methods:

  • Genome-wide binding mapping in vivo.
  • Identification of direct gene targets using transcriptomic analysis.
  • Functional assays including rescue experiments and analysis of regulatory elements.

Main Results:

  • Identified 6,396 direct targets of CFI-1, predominantly neuronal terminal differentiation markers.
  • Demonstrated CFI-1 acts as a direct activator in head sensory neurons and a direct repressor in motor neurons.
  • Uncovered the necessity of proximal binding sites and histone methyltransferase activity for glr-4 repression and the importance of ARID domains and REKLES for CFI-1 function.

Conclusions:

  • A single ARID3 protein, CFI-1, employs distinct regulatory strategies to control terminal differentiation in different neuron types.
  • This highlights context-dependent mechanisms of transcription factor action in neuronal development.