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

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 <i>ztf-11</i> (<i>Z</i>inc-finger <i>T</i>ranscription <i>F</i>actor-11), the sole <i>Caenorhabditis elegans</i> 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. <i>ztf-11</i> is exclusively expressed in all neuronal precursors with remarkable specificity at single-cell resolution. Loss of <i>ztf-11</i> leads to upregulation of non-neuronal genes and reduced neurogenesis. Ectopic expression of <i>ztf-11</i> 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.