eLife (Aug 2019)

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 K Xiang,
  • Zhirong Bao,
  • Kang Shen

DOI
https://doi.org/10.7554/eLife.46703
Journal volume & issue
Vol. 8

Abstract

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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.

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