Transcription factor SP1 regulates mouse embryonic development by targeting developmental genes

Wen Yuting; Shen Xipeng; Li Wensi; Xiang Yunlong

doi:10.13406/j.cnki.cyxb.003833

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Transcription factor SP1 regulates mouse embryonic development by targeting developmental genes

Basic research | 更新时间：2026-06-11

- Transcription factor SP1 regulates mouse embryonic development by targeting developmental genes
- Journal of Chongqing Medical University Vol. 51, Issue 6, Pages: 844-849(2026)
- 作者机构：
  
  重庆医科大学基础医学院医学表观遗传学研究中心，重庆 400016
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003833
  CLC： R394.1
- Received：14 January 2025，
  
  Revised：2025-03-11，
  
  Published：28 June 2026
- 稿件说明：
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文禹婷,申喜鹏,李文思等.转录因子SP1靶向发育基因调控小鼠胚胎发育[J].重庆医科大学学报,2026,51(06):844-849.

Wen Yuting,Shen Xipeng,Li Wensi,et al.Transcription factor SP1 regulates mouse embryonic development by targeting developmental genes[J].Journal of Chongqing Medical University,2026,51(06):844-849.
文禹婷,申喜鹏,李文思等.转录因子SP1靶向发育基因调控小鼠胚胎发育[J].重庆医科大学学报,2026,51(06):844-849. DOI： 10.13406/j.cnki.cyxb.003833.

Wen Yuting,Shen Xipeng,Li Wensi,et al.Transcription factor SP1 regulates mouse embryonic development by targeting developmental genes[J].Journal of Chongqing Medical University,2026,51(06):844-849. DOI： 10.13406/j.cnki.cyxb.003833.

摘要

目的

探究转录因子特异性蛋白1（specificity protein 1，SP1）对小鼠植入后胚胎发育的转录调控机制。

方法

收集受精后第7.5天的小鼠植入后早期胚胎，利用胚层分离技术获取外胚层（ectoderm，Ect）、中胚层（mesoderm，Mes）、内胚层（endoderm，End）、原条（primitive streak，PS）与胚外外胚层（extraembryonic ectoderm，ExE）组织；采用染色质免疫共沉淀测序（chromatin immunoprecipitation-sequencing，ChIP-seq）检测SP1在基因组的分布情况；利用CRISPR/Cas9基因编辑结合受精卵电转核酸酶（zygote electroporation of nucleases，ZEN）技术制备

Sp1

敲除的胚胎；采用Smart-seq2检测胚胎的mRNA表达水平并分析对照组与

Sp1

敲除的胚胎中各胚层的差异表达基因（differentially expressed genes，DEGs）；采用基因本体（gene ontology，GO）富集分析对DEGs进行功能聚类；结合ChIP-seq和RNA-seq数据鉴定SP1调控各胚层发育的潜在下游基因。

结果

SP1在各胚层中均有表达，其信号峰大量富集于基因启动子区，在基因主体与基因间区分布较少；敲除

Sp1

导致RNA表达变化的基因数目在Mes、ExE中较多，功能聚类显示其中表达下调的基因与器官发育、形态发生以及血管生成等生物学进程相关；进一步结合SP1的基因组分布，鉴定出SP1调节胚层发育的潜在关键靶基因，如

Gbx2

、

Vim

等。

结论

SP1结合胚层特异性的发育基因启动子，可能通过调控其转录水平进而影响胚层分化。

Abstract

Objective

To investigate transcriptional regulatory mechanisms by which the transcription factor specificity protein 1 （SP1） regulates post-implantation embryonic development in mice.

Methods

Early-stage post-implantation mouse embryos 7.5 days after fertilization were collected. Embryonic germ layer separation techniques were employed to isolate the ectoderm（Ect），mesoderm （Mes），endoderm（End），primitive streak（PS），and extra-embryonic ectoderm（ExE）. Chromatin immunoprecipitation sequencing （ChIP-seq） was performed to map the genome-wide binding profile of SP1.

Sp1

-deficient embryos were prepared through CRISPR/Cas9-mediated gene editing coupled with zygote electroporation of nucleases. Smart-seq2 was applied for embryonic mRNA profiling and identification of differentially expressed genes（DEGs） across the embryonic layers between control and

Sp1

-deficient embryos. Gene Ontology enrichment analysis was conducted to cluster DEGs by function. Finally，ChIP-seq and RNA-seq datasets were combined to identify potential downstream targets regulated by SP1 during embryonic layer development.

Results

SP1 was expressed across all the embryonic layers，with its binding sites predominantly enriched in promoter regions while less abundant in gene bodies and intergenic regions.

Sp1

knockout led to a greater number of genes with altered RNA expression in the Mes and ExE. The GO analysis revealed that the downregulated genes were involved in organ development，morphogenesis，and angiogenesis. With the genome-wide SP1 binding profile，potential key targets regulated by SP1 in embryonic layer development were identified，which included

Gbx2

and

Vim

Conclusion

SP1 binds to the promoters of germ layer-specific developmental genes，potentially modulating their transcriptional activity and thereby influencing embryonic layer specification.

关键词

Keywords

references

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