Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood. We chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and iridophores to identify epigenetic determinants shaping cell type-specific gene expression. Motif enrichment in the epigenetically dynamic regions reveals putative transcription factors that might be responsible for driving pigment cell identity. Through this effort, in the relatively uncharacterized iridophores, we validate alx4a as a necessary and sufficient transcription factor for iridophore differentiation and present evidence on alx4a’s potential regulatory role in guanine synthesis pathway. Pigment cell fate is marked by substantial DNA demethylation events coupled with dynamic chromatin accessibility to potentiate gene regulation through cis-regulatory control. Here, we provide a multi-omic resource for neural crest differentiation into melanophores and iridophores. This work led to the discovery and validation of iridophore-specific alx4a transcription factor.

中文翻译：

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影响斑马鱼黑色素细胞和虹彩细胞命运的表观遗传动力学

斑马鱼色素细胞分化为研究细胞命运进展提供了一个有吸引力的模型，因为神经嵴祖细胞产生多种细胞类型，包括两种形态不同的色素细胞：黑色黑色素细胞和反射性虹彩细胞。非平凡的经典遗传和转录组学方法揭示了驱动神经嵴衍生细胞命运决定的基本分子机制和基因调控回路。然而，表观遗传景观如何促进色素细胞分化，特别是在虹膜细胞命运的背景下，却知之甚少。我们绘制了表观遗传景观的全球变化，包括 DNA 甲基化和染色质可及性，在神经嵴分化为黑色素细胞和虹彩细胞的过程中，以确定塑造细胞类型特异性基因表达的表观遗传决定因素。表观遗传动态区域中的基序富集揭示了可能负责驱动色素细胞特性的推定转录因子。通过这项努力，在相对未表征的虹彩细胞中，我们验证了 alx4a 作为虹彩细胞分化的必要和充分的转录因子，并提供了关于 alx4a 在鸟嘌呤合成途径中的潜在调节作用的证据。色素细胞命运的标志是大量的 DNA 去甲基化事件以及动态染色质可及性，以通过顺式调节控制增强基因调节。在这里，我们为神经嵴分化为黑色素细胞和虹彩细胞提供了多组学资源。