Elsevier

Developmental Biology

Volume 433, Issue 1, 1 January 2018, Pages 61-74
Developmental Biology

Original research article
Nasal and otic placode specific regulation of Sox2 involves both activation by Sox-Sall4 synergism and multiple repression mechanisms

https://doi.org/10.1016/j.ydbio.2017.11.005Get rights and content
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Highlights

  • The NOP1 enhancer of the Sox2 gene is active in nasal and otic placodes.

  • Repressing and activating elements cooperatively regulate NOP1 specificity.

  • The synergistic actions of Sall4 and SoxB1/E represent a core activation mechanism for NOP1.

  • CACCT/CACCTG-binding repressors confine the enhancer activity to the nasal and otic placodes.

Abstract

Transcription factor gene Sox2 is expressed throughout sensory development, but the enhancers that regulate the gene vary depending on the developmental stages and tissues. To gain new insights into the gene regulatory network in sensory placode specification, regulation of the nasal-otic bispecific NOP1 enhancer of Sox2 was investigated in chicken embryos. Deletion and mutational analyses using electroporation showed that transcriptional repression mechanisms in combination with activation mechanisms determine placodal specificity. Activation of the NOP1 enhancer involves synergistic action by Sall4 and SoxB1/SoxE factors that bind to the adjacent sites. Deletion of repressive elements resulted in widening of the tissue area for enhancer activity to a region where the expression of Sall4 and SoxB1/E overlaps, e.g., the CNS and neural crest. Among multiple repressive elements that contribute to the placodal confinement of the NOP1 enhancer activity, CACCT/CACCTG motifs bound by Zeb/Snail family repressors play important roles. Overexpression of δEF1 (Zeb1) or Snail2 (Slug) strongly inhibited NOP1 activity. These data indicate that both activation by Sall4-Sox synergism and multiple repression mechanisms involving Zeb/Snail factors are essential for Sox2 regulation to be confined to the nasal and otic placodes.

Keywords

Sensory development
Nasal and otic placodes
Sox2 NOP1 enhancer
Sall4
Sox factors
Zeb and Snail factors

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