A Myt1 family transcription factor defines neuronal fate by repressing non-neuronal genes

Joo Lee, Caitlin A. Taylor, Kristopher M. Barnes, Ao Shen, Emerson V. Stewart, Allison Chen, Yang Kevin Xiang, Zhirong Bao, Kang Shen

Research output: Contribution to journalArticle

Abstract

Cellular differentiation requires both activation of target cell transcriptional programs and repression of non-target cell programs. The Myt1 family of zinc finger transcription factors contributes to fibroblast to neuron reprogramming in vitro. Here, we show that ztf-11 (Zinc-finger Transcription Factor-11), the sole Caenorhabditis elegans Myt1 homolog, is required for neurogenesis in multiple neuronal lineages from previously differentiated epithelial cells, including a neuron generated by a developmental epithelial-to-neuronal transdifferentiation event. ztf-11 is exclusively expressed in all neuronal precursors with remarkable specificity at single-cell resolution. Loss of ztf-11 leads to upregulation of non-neuronal genes and reduced neurogenesis. Ectopic expression of ztf-11 in epidermal lineages is sufficient to produce additional neurons. ZTF-11 functions together with the MuvB corepressor complex to suppress the activation of non-neuronal genes in neurons. These results dovetail with the ability of Myt1l (Myt1-like) to drive neuronal transdifferentiation in vitro in vertebrate systems. Together, we identified an evolutionarily conserved mechanism to specify neuronal cell fate by repressing non-neuronal genes.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Aug 6 2019

Fingerprint

Zinc Fingers
Zinc
Transcription Factors
Genes
Neurons
Neurogenesis
Chemical activation
Co-Repressor Proteins
Caenorhabditis elegans
Fibroblasts
Vertebrates
Up-Regulation
Epithelial Cells
In Vitro Techniques

Keywords

  • C. elegans
  • developmental biology
  • genetics
  • genomics
  • MuvB complex
  • Myt1
  • neurogenesis
  • neuronal differentiation
  • transcriptional repression
  • ZTF-11

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Lee, J., Taylor, C. A., Barnes, K. M., Shen, A., Stewart, E. V., Chen, A., ... Shen, K. (2019). A Myt1 family transcription factor defines neuronal fate by repressing non-neuronal genes. eLife, 8. https://doi.org/10.7554/eLife.46703

A Myt1 family transcription factor defines neuronal fate by repressing non-neuronal genes. / Lee, Joo; Taylor, Caitlin A.; Barnes, Kristopher M.; Shen, Ao; Stewart, Emerson V.; Chen, Allison; Xiang, Yang Kevin; Bao, Zhirong; Shen, Kang.

In: eLife, Vol. 8, 06.08.2019.

Research output: Contribution to journalArticle

Lee, J, Taylor, CA, Barnes, KM, Shen, A, Stewart, EV, Chen, A, Xiang, YK, Bao, Z & Shen, K 2019, 'A Myt1 family transcription factor defines neuronal fate by repressing non-neuronal genes', eLife, vol. 8. https://doi.org/10.7554/eLife.46703
Lee, Joo ; Taylor, Caitlin A. ; Barnes, Kristopher M. ; Shen, Ao ; Stewart, Emerson V. ; Chen, Allison ; Xiang, Yang Kevin ; Bao, Zhirong ; Shen, Kang. / A Myt1 family transcription factor defines neuronal fate by repressing non-neuronal genes. In: eLife. 2019 ; Vol. 8.
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