1. A Myt1 family transcription factor defines neuronal fate by repressing non-neuronal genes.
- Author
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Lee, Joo, Taylor, Caitlin A, Barnes, Kristopher M, Shen, Ao, Stewart, Emerson V, Chen, Allison, Xiang, Yang K, Bao, Zhirong, and Shen, Kang
- Subjects
Neurons ,Epithelial Cells ,Animals ,Caenorhabditis elegans ,Trans-Activators ,Caenorhabditis elegans Proteins ,Cell Differentiation ,Gene Expression Regulation ,C. elegans ,MuvB complex ,Myt1 ,ZTF-11 ,developmental biology ,genetics ,genomics ,neurogenesis ,neuronal differentiation ,transcriptional repression ,Biochemistry and Cell Biology - 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.
- Published
- 2019