Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos.
Lijia LiFangnong LaiXiaoyu HuBofeng LiuXukun LuZili LinLing LiuYunlong XiangTristan FrumMichael A HalbisenFengling ChenQiang FanAmy RalstonWei XiePublished in: Science (New York, N.Y.) (2023)
Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed pluripotency regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding from embryonic day 3.5 (E3.5) to E7.5 in the mouse. In E3.5 inner cell mass (ICM), SOX2 regulates the ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, SOX2 occupies preaccessible enhancers in part opened by early-stage expressing TFs TFAP2C and NR5A2. SOX2 then widely redistributes when cells adopt naive and formative pluripotency by opening enhancers or poising them for rapid future activation. Hence, multifaceted pioneer TF-enhancer interaction underpins pluripotency progression in embryos, including a distinctive state in E3.5 ICM that bridges totipotency and pluripotency.
Keyphrases
- transcription factor
- embryonic stem cells
- dna binding
- cell fate
- stem cells
- induced apoptosis
- early stage
- cell cycle arrest
- genome wide identification
- gene expression
- squamous cell carcinoma
- single cell
- endothelial cells
- oxidative stress
- signaling pathway
- hiv infected
- dna damage
- cell therapy
- atomic force microscopy
- endoplasmic reticulum stress
- diabetic retinopathy
- quantum dots
- antiretroviral therapy
- locally advanced