The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans

Cell identity is characterized by a distinct combination of gene expression, cell morphology, and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remainin...

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Main Authors: Josh Saul, Takashi Hirose, H Robert Horvitz
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2022-02-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/74557
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author Josh Saul
Takashi Hirose
H Robert Horvitz
author_facet Josh Saul
Takashi Hirose
H Robert Horvitz
author_sort Josh Saul
collection DOAJ
description Cell identity is characterized by a distinct combination of gene expression, cell morphology, and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here, we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in later larval stage and adult worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.
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spelling doaj.art-d0f22d1bc5e548f394b11541888021a92022-12-22T04:32:49ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.74557The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegansJosh Saul0https://orcid.org/0000-0003-4193-497XTakashi Hirose1H Robert Horvitz2https://orcid.org/0000-0002-9964-9613Department of Biology, Massachusetts Institute of Technology, Howard Hughes Medical Institute, Cambridge, United StatesDepartment of Biology, Massachusetts Institute of Technology, Howard Hughes Medical Institute, Cambridge, United StatesDepartment of Biology, Massachusetts Institute of Technology, Howard Hughes Medical Institute, Cambridge, United StatesCell identity is characterized by a distinct combination of gene expression, cell morphology, and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here, we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in later larval stage and adult worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.https://elifesciences.org/articles/74557C. eleganscell-identity maintenancetranscriptional corepressorcell fate
spellingShingle Josh Saul
Takashi Hirose
H Robert Horvitz
The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans
eLife
C. elegans
cell-identity maintenance
transcriptional corepressor
cell fate
title The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans
title_full The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans
title_fullStr The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans
title_full_unstemmed The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans
title_short The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in Caenorhabditis elegans
title_sort transcriptional corepressor ctbp 1 acts with the sox family transcription factor egl 13 to maintain aia interneuron cell identity in caenorhabditis elegans
topic C. elegans
cell-identity maintenance
transcriptional corepressor
cell fate
url https://elifesciences.org/articles/74557
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