转录因子结合表面的辅激剂p300是需要血液形成的血液形成
Lawryn H Kasper1, Fayçal Boussouar, Paul A Ney
1Department of Biochemistry, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38105, USA.
Nature
|October 18, 2002
概括
协同激活剂CBP和p300的KIX域在小鼠发育中起着不同的作用. 破坏p300的KIX域会损害血细胞的形成,而CBP的KIX域突变的影响很小.
科学领域:
- 分子生物学分子生物学
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- CBP (CREB结合蛋白) 和p300是参与基因调节的关键联合激活剂.
- 这些蛋白质具有适应分子和蛋白质乙转移酶功能,对于正常发育至关重要.
- CBP和p300的突变与各种癌症有关,包括造血和上皮瘤.
研究的目的:
- 为了研究CBP和p300联合激活剂的体内功能.
- 确定CBP和p300的KIX域在哺乳动物发育中的重要作用.
- 阐明CBP和p300 KIX域在造血调节中的特定功能.
主要方法:
- 在CBP和p300的KIX域中产生具有向点突变的小鼠.
- 对突变小鼠的造血发育和多血统缺陷的分析.
- 涉及c-Myb和p300 KIX域突变的遗传相互作用研究.
主要成果:
- 患有 p300 KIX 域中断的小鼠表现出严重的多系血缺陷,包括贫血和B细胞缺乏.
- 在CBP KIX域中的突变不会在小鼠中引起显著的发育异常.
- c-Myb和p300 KIX域突变之间的协同基因相互作用突出显示了c-Myb与p300结合在巨核细胞发育中的关键作用.
结论:
- CBP和p300的KIX域在体内具有非冗余和对比的功能,特别是在血液形成中.
- 转录因子c-Myb与p300 KIX域的结合对于巨核细胞的发育和功能至关重要.
- 这些发现揭示了高度相关的协同激活剂在调节复杂的生物过程中的特殊作用.
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