Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex

Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex
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DOI:
10.1101/gad.10.24.3202
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发表时间:
1996-12-15
影响因子:
10.5
通讯作者:
Schedl, P
Schedl, P
中科院分区:
生物学1区
文献类型:
--
作者:
Hagstrom, K;Muller, M;Schedl, P

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bithorax复合体中的Fab-7缺失具有一种新的功能获得表型,通常将第11段(PS11)转化为PS12身份。遗传分析表明,去除Fab-7元件导致iab-6 (PS11)和iab-7 (PS12)顺式调控结构域融合为一个单一的调控结构域,不适当地调控PS11中的腹腔b。这导致了一种假设,即Fab-7是染色质结构域边界,其正常功能是确保ab-6和ab-7顺式调控结构域的自主活性。我们使用几种不同的增强子阻断试验来证明Fab-7具有预期的结构域边界的绝缘特性。我们定义了一个足以阻断增强子的最小Fab-7片段,并证明它与相邻的polycomb依赖消声器完全不同。我们将Fab-7与su(Hw)绝缘子元件进行了比较,发现Fab-7增强子阻断了su(Hw)蛋白的5到12个重复结合位点之间的活性。这些结果支持了Fab-7在bithorax复合物中作为结构域边界的模型,使Fab-7成为已知的第一个在体内具有基本功能的边界元素之一。
Fab-7 deletions in the bithorax complex have a novel gain-of-function phenotype, typically transforming parasegment 11 (PS11) into PS12 identity. Genetic analysis indicates that removal of the Fab-7 element results in the fusion of the iab-6 (PS11) and iab-7 (PS12) cis-regulatory domains into a single regulatory domain that inappropriately regulates Abdominal-B in PS11. This has led to the hypothesis that Fab-7 is a chromatin domain boundary that normally functions to ensure the autonomous activity of the iab-6 and iab-7 cis-regulatory domains. We use several different enhancer blocking assays to demonstrate the Fab-7 has the insulating properties expected of a domain boundary. We define a minimal fragment of Fab-7 sufficient for enhancer blocking, and demonstrate that it is completely distinct from an adjacent Polycomb-dependent silencer. We compare Fab-7 to the su(Hw) insulator element, and show that Fab-7 enhancer blocking activity in intermediate between that of five and twelve reiterated binding sites for the Su(Hw) protein. These results support the model that Fab-7 functions as a domain boundary within the context of the bithorax complex, making Fab-7 one of the first boundary elements that is known to have an essential function in vivo.