遥远的全球控制区域对于小鼠和人类面发育过程中前部HOXA基因的正常表达至关重要
Andrea Wilderman1, Eva D'haene2, Machteld Baetens2
1Graduate Program UConn Health, Farmington, CT, USA.
Nature communications
|January 3, 2024
概括
科学家们发现了一个关键的超级增强器区域调节面部发育. 它的干扰会在小鼠和人类中引起严重的面异常和口面裂,突出显示它在出生缺陷中的作用.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 人类遗传学 人类遗传学
背景情况:
- 面异常占出生缺陷的很大一部分.
- 超级增强剂对细胞身份至关重要,但在胚胎发育中未被充分探索.
- 通过增强剂精确的时空基因表达对于面部发育至关重要.
研究的目的:
- 在人类胚胎面组织中确定新的超强增强器区域.
- 研究特定非编码区域在面发育和疾病中的作用.
- 确定该监管区域的副本数变异的致病潜力.
主要方法:
- 在人类胚胎面组织中识别超强增强器区域.
- 在人类和小鼠模型中分析非编码区域和HOXA基因集群之间的远程相互作用.
- 对缺乏已识别的超级增强剂的小鼠进行表型分析.
- 对人类患者的基因分析,在超级增强器区域出现了新的拷贝数变化.
主要成果:
- 在人类胚胎面组织中确定了一个独特的超级增强器区域.
- 这个区域与前方HOXA基因集群相互作用.
- 缺乏超级增强剂的小鼠表现出围产死亡率,头骨缺陷和面腔裂.
- 两个患有严重面异常的人类病例在这个超级增强器中出现了新的副本数量变化.
结论:
- 已经确定了一个关键的非编码位置控制区域,在面发育中调节前部HOXA基因.
- 这种超级增强器的破坏是致病的,导致严重的面异常.
- 这一区域的复制号变化与人类面出生缺陷有关.
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