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组合转录因子在开放染色质上的活性诱导脊椎动物胚胎的异质性。

Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates.

机构信息

Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands.

Biomedical Pioneering Innovation Center, Peking University, Beijing, China.

出版信息

EMBO J. 2021 May 3;40(9):e104913. doi: 10.15252/embj.2020104913. Epub 2021 Feb 8.

DOI:10.15252/embj.2020104913
PMID:33555045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8090851/
Abstract

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.

摘要

在脊椎动物原肠胚形成过程中，中胚层在多能细胞中被诱导，同时伴随着背腹模式形成和背轴的建立。我们应用单细胞染色质可及性和转录组分析来探索非洲爪蟾 Xenopus tropicalis 原肠胚形成过程中细胞异质性的出现。转录失活的谱系限制基因在动物帽中表现出相对开放的染色质，而背缘区细胞的染色质可及性更能反映转录活性。我们描述了单细胞轨迹，并在早期原肠胚中鉴定出头和躯干组织者细胞簇。通过整合染色质可及性和转录组数据，我们推断了单个细胞簇中转录因子的活性，并在动物帽中单独或组合测试了组织者表达的转录因子的活性。Foxb1 和 Eomes 组合诱导的表达谱最接近观察到的头部组织者。由 Eomes、Otx2 或 Irx3-Otx2 组合诱导的基因富含母体调控的 H3K4me3 修饰，而由 Lhx8 诱导的基因更频繁地被合子控制的 H3K4me3 标记。总之，我们的结果表明，转录因子以组合的方式在通常开放的染色质中合作，以协调合子基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/5aaf068e74b6/EMBJ-40-e104913-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/7c66a5d7c8ba/EMBJ-40-e104913-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/9192f5c481bc/EMBJ-40-e104913-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/caa9644c9f8e/EMBJ-40-e104913-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/f35209c29235/EMBJ-40-e104913-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/3eeafe7fc8da/EMBJ-40-e104913-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/c6775fcbb58c/EMBJ-40-e104913-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/9e55843da26b/EMBJ-40-e104913-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/bbc6b236f592/EMBJ-40-e104913-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/6cc9fd13fae9/EMBJ-40-e104913-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/7c66a5d7c8ba/EMBJ-40-e104913-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/9192f5c481bc/EMBJ-40-e104913-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/caa9644c9f8e/EMBJ-40-e104913-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/f35209c29235/EMBJ-40-e104913-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/3eeafe7fc8da/EMBJ-40-e104913-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/c6775fcbb58c/EMBJ-40-e104913-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/3da711200068/EMBJ-40-e104913-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e669/8090851/5aaf068e74b6/EMBJ-40-e104913-g004.jpg

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