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

eLife

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[1] Department of Biochemistry, Stanford University, Stanford, United States;Howard Hughes Medical Institute, Stanford University, Stanford, United States;Department of Biology, Stanford University, Stanford, United States;Department of Pharmacology, University of California, Davis, Davis, United States;Developmental Biology Program, Sloan-Kettering Institute, New York, United States;Howard Hughes Medical Institute, Stanford University, Stanford, United States;Department of Biology, Stanford University, Stanford, United States;

关键词: ZTF-11;    Myt1;    neurogenesis;    MuvB complex;    transcriptional repression;    neuronal differentiation;    C. elegans;   

DOI  :  10.7554/eLife.46703

来源: publisher

【 摘 要 】

10.7554/eLife.46703.001Cellular 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.

【 授权许可】

CC BY