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EMBO J 2021 May 03;409:e104913. doi: 10.15252/embj.2020104913.
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Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates.

Bright AR , van Genesen S , Li Q , Grasso A , Frölich S , van der Sande M , van Heeringen SJ , Veenstra GJC .

During vertebrate gastrulation, mesoderm is induced in pluripotent cells, concomitant with dorsal-ventral patterning and establishing of the dorsal axis. We applied single-cell chromatin accessibility and transcriptome analyses to explore the emergence of cellular heterogeneity during gastrulation in Xenopus tropicalis. Transcriptionally inactive lineage-restricted genes exhibit relatively open chromatin in animal caps, whereas chromatin accessibility in dorsal marginal zone cells more closely reflects transcriptional activity. We characterized single-cell trajectories and identified head and trunk organizer cell clusters in early gastrulae. By integrating chromatin accessibility and transcriptome data, we inferred the activity of transcription factors in single-cell clusters and tested the activity of organizer-expressed transcription factors in animal caps, alone or in combination. The expression profile induced by a combination of Foxb1 and Eomes most closely resembles that observed in the head organizer. Genes induced by Eomes, Otx2, or the Irx3-Otx2 combination are enriched for maternally regulated H3K4me3 modifications, whereas Lhx8-induced genes are marked more frequently by zygotically controlled H3K4me3. Taken together, our results show that transcription factors cooperate in a combinatorial fashion in generally open chromatin to orchestrate zygotic gene expression.

PubMed ID: 33555045
PMC ID: PMC8090851
Article link: EMBO J
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: cer1 chrd crebbp crx ctcf dkk1 dmbx1 eomes fgf8 foxa1 foxb1 foxd4l1.1 foxi4.2 foxj1 frzb fst gata3 gata4 grhl1 grhl3 gsc irx1 irx3 klf2 klf5 lhx1 lhx8 mespb mix1 mixer nog otx2 pcdh8 pou5f3 pou5f3.3 snai1 sox11 sox17a sox17b.1 sox2 sp5 tbxt tfap2a upk3b vegt ventx1 ventx1.2 ventx2 wnt11b zic1 zic3
GO keywords: axis specification

GEO Series: GSE145619: Xenbase,  NCBI

Article Images: [+] show captions
References [+] :
Agius, Endodermal Nodal-related signals and mesoderm induction in Xenopus. 2000, Pubmed, Xenbase