一个多重超增强器区域建立了TAD间的相互作用,并控制了头骨神经中的霍克萨功能
Sandra Kessler1,2, Maryline Minoux1,3, Onkar Joshi1
1Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland.
Nature communications
|June 5, 2023
概括
超级增强剂 (SE) 在面部发育过程中调节神经细胞 (CNCC) 中的基因表达. 这些SE可以克服拓障碍来控制基因表达,影响耳朵和面部结构的形成.
科学领域:
- 基因组学就是基因组学.
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 增强剂-促进剂相互作用通常局限于拓关联域 (TAD).
- 超级增强剂 (SE) 是调节高基因表达的增强剂集群.
- 在面发育中SEs的作用仍然在很大程度上未被探索.
研究的目的:
- 在小鼠神经细胞 (CNCCs) 中识别全基因组超级增强剂 (SE).
- 调查SEs对面发育的拓监管影响,特别关注Hoxa基因.
主要方法:
- 在小鼠CNCC中对假定SE的全基因组鉴定.
- 对增强剂-促进剂相互作用和TAD绝缘的分析.
- 基因删除研究 (HIRE1,HIRE2) 在Hoxa2哈普洛不充分模型中.
主要成果:
- 在CNCC中确定了2232个SE,其中147个向基因对面部发育至关重要.
- 在PA2 CNCC中发现了一个SE区域 (HIRE1/HIRE2),该区域与Hoxa2相互作用,这对耳朵发育至关重要.
- 删除HIRE2导致微病;删除HIRE1模仿了Hoxa2淘汰赛,影响PA3/PA4 CNCC和Hoxa基因表达.
结论:
- SEs可以超越TAD绝缘,以细胞类型特定的方式调节基因表达.
- 在面发育过程中,SEs在前部霍克萨基因的线性表达中发挥着关键作用.
- 这项研究揭示了对SE介导的面形态发生调节的新见解.
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