Displacement of D1, HP1 and topoisomerase II from satellite heterochromatin by a specific polyamide
Displacement of D1, HP1 and topoisomerase II from satellite heterochromatin by a specific polyamide
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DOI：
10.1038/sj.emboj.7601125
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发表时间：
2006-06-07
期刊：
影响因子：
11.4
通讯作者：
Kas, Emmanuel
中科院分区：
文献类型：
--
作者：
Blattes, Roxane;Monod, Caroline;Kas, Emmanuel
中心异染色质DNA卫星的功能很难用传统的分子生物学工具来评估。利用化学方法，我们证明了合成聚酰胺可以专门针对果蝇富含at的卫星重复序列来研究这些序列的功能。结合x染色体1.688 g/cm(3) satellite III （SAT III）的P9聚酰胺取代了D1蛋白。这种位移反过来导致HP1和拓扑异构酶II从SAT III中选择性丢失，而这些蛋白质仍然结合到邻近的rDNA重复序列和其他不被P9靶向的区域。相反，P31聚酰胺靶向（AAGAG） n卫星V重复序列导致HP1从这些序列中位移，表明HP1与染色质的相互作用对dna结合配体敏感。饲喂P9可抑制白斑成虫的位置效应杂色表型。我们认为这种影响是由于异染色质蛋白D1， HP1和拓扑异构酶II从SAT III中移位，从而导致染色质随机打开和附近白色基因的脱沉默。
The functions of DNA satellites of centric heterochromatin are difficult to assess with classical molecular biology tools. Using a chemical approach, we demonstrate that synthetic polyamides that specifically target AT-rich satellite repeats of Drosophila melanogaster can be used to study the function of these sequences. The P9 polyamide, which binds the X-chromosome 1.688 g/cm(3) satellite III (SAT III), displaces the D1 protein. This displacement in turn results in a selective loss of HP1 and topoisomerase II from SAT III, while these proteins remain bound to the adjacent rDNA repeats and to other regions not targeted by P9. Conversely, targeting of (AAGAG) n satellite V repeats by the P31 polyamide results in the displacement of HP1 from these sequences, indicating that HP1 interactions with chromatin are sensitive to DNA-binding ligands. P9 fed to larvae suppresses the position-effect variegation phenotype of white-mottled adult flies. We propose that this effect is due to displacement of the heterochromatin proteins D1, HP1 and topoisomerase II from SAT III, hence resulting in stochastic chromatin opening and desilencing of the nearby white gene.