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Gene regulatory networks (GRNs) involve highly combinatorial interactions between transcription factors and short sequence motifs in cis-regulatory modules of target genes to control cellular phenotypes. The GRNs specifying most cell types are largely unknown and are the subject of wide interest. A catalog of transcription factors is a valuable tool toward obtaining a deeper understanding of the role of these critical effectors in any biological setting. Here we present a comprehensive catalog of the transcription factors for the diploid frog Xenopus tropicalis. We identify 1235 genes encoding DNA-binding transcription factors, comparable to the numbers found in typical mammalian species. In detail, the repertoire of X. tropicalis transcription factor genes is nearly identical to human and mouse, with the exception of zinc finger family members, and a small number of species/lineage-specific gene duplications and losses relative to the mammalian repertoires. We applied this resource to the identification of transcription factors differentially expressed in the early gastrula stage embryo. We find transcription factor enrichment in Spemann's organizer, the ventral mesoderm, ectoderm and endoderm, and report 218 TFs that show regionalized expression patterns at this stage. Many of these have not been previously reported as expressed in the early embryo, suggesting thus far unappreciated roles for many transcription factors in the GRNs regulating early development. We expect our transcription factor catalog will facilitate myriad studies using Xenopus as a model system to understand basic biology and human disease.
Fig. 1.
Transcription factor expression dynamics during early development. A. Heat-map of TF expression over the first 66 hours post fertilization. TFs were clustered on expression profiles and ordered according their average expression time. Vertical gray rectangles identify clusters. B. DBD families present in each TF are depicted as colored circles (only for those with significant family enrichment are shown) along the same horizontal lines as the expression profiles of the corresponding TFs. C. DBD family enrichment clusters (statistically significant with FDR<0.1) are represented as rectangles.
Fig. 2.
Distribution of TF gene expression levels in the early gastrula is indistinguishable from expression of all genes. The frequency of appearance of transcription factors (right vertical axis) and all genes (left vertical axis) is plotted as a function of expression level. The two distributions are nearly identical.
Fig. 3.
Gastrula dissection strategy and validation by marker gene expression in RNA-seq data. A. Illustration shows the locations of eyebrow hair knife cuts (dotted lines) for early gastrula dissections. Left shows a sagittal view while right shows a vegetal view. Dorsal is to the right. B. A heat map from RNA-seq data shows the relative expression of various marker genes in the different dissected embryo fragments. Abbr. AC, animal cap; DMZ, dorsal marginal zone; LMZ, lateral marginal zone; VMZ, ventral marginal zone; VEG, vegetal mass.
Fig. 4.
Spatial localizations of transcription factor RNAs derived from RNA-seq. A heatmap is shown to depict the spatial expression of differentially expressed TFs in the early gastrula. TF differential expression was determined between any comparison of two embryo fragments (posterior probability ≥0.95). The expression values are plotted as the z-score of each gene across embryo fragments. The labels (e.g. endoderm, ventral mesoderm) are the inferred predominant expression pattern in each major branch in the dendrogram.
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