A novel role for the histone acetyltransferase Hat1 in the CENP-A/CID assembly pathway in Drosophila melanogaster
A novel role for the histone acetyltransferase Hat1 in the CENP-A/CID assembly pathway in Drosophila melanogaster
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DOI：
10.1093/nar/gkv1235
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发表时间：
2016-03-18
影响因子：
14.9
通讯作者：
Lusser, Alexandra
中科院分区：
文献类型：
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作者：
Boltengagen, Mark;Huang, Anming;Lusser, Alexandra
CENP-A掺入到着丝粒染色质中是动粒形成的必要先决条件。然而，控制这一过程的分子机制在不同的生物体中惊人地不同。虽然CENP-A加载机制已在哺乳动物中进行了一些详细的研究，但我们对果蝇中CENP-A/Cid加载途径的理解仍然存在很大的差距。在这里，我们报告的表征和描绘至少三种不同的CENP-A预加载复合物在果蝇。两种复合物含有CENP-A分子伴侣CAL 1、FACT和/或Caf 1/Rbap 48。值得注意的是，我们确定了一种新的复合物组成的组蛋白乙酰转移酶Hat 1，Caf 1和CENP-A/H4。我们表明，Hat 1是正确的CENP-A载入染色质所必需的，因为在S2细胞中敲低导致新合成的CENP-A的掺入减少。此外，我们证明CENP-A/Cid通过N-末端区域与HAT 1复合物相互作用，该区域在细胞质中乙酰化，但不在细胞核CENP-A中。由于Hat 1不负责CENP-A/Cid的乙酰化，因此这些结果表明Hat 1具有组蛋白乙酰转移酶活性独立的护送功能。因此，我们的研究结果指向新合成的CENP-A和典型组蛋白的复杂加工途径之间有趣的类比。
The incorporation of CENP-A into centromeric chromatin is an essential prerequisite for kinetochore formation. Yet, the molecular mechanisms governing this process are surprisingly divergent in different organisms. While CENP-A loading mechanisms have been studied in some detail in mammals, there are still large gaps to our understanding of CENP-A/Cid loading pathways in Drosophila. Here, we report on the characterization and delineation of at least three different CENP-A preloading complexes in Drosophila. Two complexes contain the CENP-A chaperones CAL1, FACT and/or Caf1/Rbap48. Notably, we identified a novel complex consisting of the histone acetyltransferase Hat1, Caf1 and CENP-A/H4. We show that Hat1 is required for proper CENP-A loading into chromatin, since knock-down in S2 cells leads to reduced incorporation of newly synthesized CENP-A. In addition, we demonstrate that CENP-A/Cid interacts with the HAT1 complex via an N-terminal region, which is acetylated in cytoplasmic but not in nuclear CENP-A. Since Hat1 is not responsible for acetylation of CENP-A/Cid, these results suggest a histone acetyltransferase activity-independent escort function for Hat1. Thus, our results point toward intriguing analogies between the complex processing pathways of newly synthesized CENP-A and canonical histones.