多个cis-regulatory元素控制不同淋巴血管床中的prox1a表达.
Virginia Panara1,2, Hujun Yu3,4, Di Peng1
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75185, Sweden.
概括
研究人员发现了在发育过程中淋巴内皮细胞 (LEC) 中Prox1基因表达是如何控制的. 他们确定了特定的DNA区域,称为增强剂,调节Prox1,影响淋巴血管的形成和功能.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 与普罗斯佩罗相关的Homeobox 1 (Prox1) 是淋巴内皮细胞 (LEC) 发育和淋巴血管形成的关键基因.
- 虽然Prox1是必不可少的,但其在LEC的上游监管机制尚未完全理解.
- 以前的研究表明,SOX18和COUP-TFII在小鼠中调节了Prox1,但在LEC中进行详细调节需要进一步调查.
研究的目的:
- 识别和描述控制斑马鱼淋巴内皮细胞中Prox1表达的调控元素.
- 了解这些调节元素在淋巴发育和功能中的作用.
主要方法:
- 利用进化保护分析和染色质可访问性数据来预测斑马鱼prox1a基因附近的潜在增强剂.
- 采用CRISPR/Cas9基因编辑来突变特定的淋巴增强剂.
- 评估了增强器删除对淋巴形态和功能的影响.
主要成果:
- 在斑马鱼prox1a基因附近确定了多重增强剂,这些增强剂在开发LEC中活跃.
- 证明了淋巴增强剂的删除会导致门形态和功能受损.
- 表明不同的增强剂集控制Prox1表达:远端增强剂驱动广泛的淋巴表达,而近端增强剂在特定的淋巴子集中改进表达.
结论:
- 斑马鱼中的Prox1a表达是由一个增强剂网络复杂地控制的.
- 光鱼特有的远端增强剂对于泛淋巴体表达至关重要.
- 脊椎动物保存的近位增强剂在提炼Prox1a表达对于特定的淋巴内皮细胞种群和功能方面发挥着作用.
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