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

Elife. 2022 Feb 4;11:e74557. doi: 10.7554/eLife.74557.

Abstract

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.

Keywords: C. elegans; cell fate; cell-identity maintenance; developmental biology; genetics; genomics; transcriptional corepressor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Differentiation
  • Gene Expression Regulation, Developmental
  • Interneurons / cytology*
  • Interneurons / physiology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • SOXD Transcription Factors / genetics
  • SOXD Transcription Factors / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • CTBP-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Repressor Proteins
  • SOXD Transcription Factors
  • Transcription Factors

Associated data

  • GEO/GSE179484
  • figshare/10.6084/m9.figshare.c.5771480.v1