Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation
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 p...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723002310 |
| _version_ | 1811155474260688896 |
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| author | Yinan Li Jayson J. Smith Filipe Marques Anthony Osuma Hsin-Chiao Huang Paschalis Kratsios |
| author_facet | Yinan Li Jayson J. Smith Filipe Marques Anthony Osuma Hsin-Chiao Huang Paschalis Kratsios |
| author_sort | Yinan Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T04:34:44Z |
| format | Article |
| id | doaj.art-240b2e275a4244f38aca9a34844f8e69 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-10T04:34:44Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-240b2e275a4244f38aca9a34844f8e692023-03-10T04:34:52ZengElsevierCell Reports2211-12472023-03-01423112220Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiationYinan Li0Jayson J. Smith1Filipe Marques2Anthony Osuma3Hsin-Chiao Huang4Paschalis Kratsios5Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; University of Chicago Neuroscience Institute, Chicago, IL 60637, USADepartment of Neurobiology, University of Chicago, Chicago, IL 60637, USA; Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USACommittee on Development, Regeneration, and Stem Cell Biology, University of Chicago, Chicago, IL 60637, USADepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723002310CP: Neuroscience |
| spellingShingle | Yinan Li Jayson J. Smith Filipe Marques Anthony Osuma Hsin-Chiao Huang Paschalis Kratsios Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation Cell Reports CP: Neuroscience |
| title | Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation |
| title_full | Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation |
| title_fullStr | Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation |
| title_full_unstemmed | Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation |
| title_short | Cell context-dependent CFI-1/ARID3 functions control neuronal terminal differentiation |
| title_sort | cell context dependent cfi 1 arid3 functions control neuronal terminal differentiation |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723002310 |
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