一个哺乳动物的三方增强剂集群控制着下丘脑Pomc表达,食物摄入量和体重
Daniela Rojo1, Clara E Hael1, Agustina Soria1,2
1Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires 1428, Argentina.
概括
科学家们发现了一种新的增强剂,nPE3,对于调节在下丘脑中的proopiomelanocortin (POMC) 基因表达至关重要. 这一发现揭示了哺乳动物对食物摄入量和体重平衡的遗传控制.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 进化生物学 进化生物学
背景情况:
- 脑下垂体的普罗皮欧梅拉诺科廷 (POMC) 神经元严格调节食物摄入量和能量平衡.
- 两个已知的增强剂,nPE1和nPE2,在弧形神经元中驱动POMC表达.
- 之前的研究表明,对于POMC表达,存在额外的监管要素.
研究的目的:
- 为了确定调节下丘脑POMC表达的新型cis作用元素.
- 研究这些元素的进化起源和功能意义.
- 阐明已识别的增强剂在控制食物摄入量和脂肪的作用.
主要方法:
- 利用分子进化分析来识别潜在的增强剂.
- 在转基因斑马鱼和小鼠中使用记者基因表达测试.
- 生成并分析了缺乏特定POMC增强剂 (nPE1,nPE2,nPE3) 的突变小鼠.
主要成果:
- 确定了一种新的哺乳动物弓形类特定的POMC增强剂,称为nPE3.3.
- nPE3含有关键转录因子 (ISL1,NKX2.1,ERα) 的结合位点.
- 废除nPE3在发育过程中显著降低POMC mRNA,在成年人中适度降低,影响食物摄入量和脂肪.
结论:
- nPE3是调节下丘脑POMC表达的三方增强剂集群的关键组成部分.
- 这种增强剂集群在哺乳动物中趋同演化,在体重恒温中起着至关重要的作用.
- 在Simiiformes (灵长类动物) 中,nPE3的丧失表明代谢调节的进化差异.
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