Promoter region-specific histone incorporation by the novel histone chaperone ANP32B and DNA-binding factor KLF5
Promoter region-specific histone incorporation by the novel histone chaperone ANP32B and DNA-binding factor KLF5
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DOI：
10.1128/mcb.01396-07
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发表时间：
2008-02-01
影响因子：
5.3
通讯作者：
Nagai, Ryozo
中科院分区：
文献类型：
--
作者：
Munemasa, Yoshiko;Suzuki, Toru;Nagai, Ryozo
真核转录中染色质的调节需要组蛋白修饰酶、核小体重塑复合物和组蛋白伴侣。启动子上组蛋白伴侣对组蛋白掺入/驱逐的特异性调节（例如区域特异性）仍然知之甚少。在本研究中，我们表明组蛋白伴侣和 DNA 结合转录因子的直接和功能性相互作用导致启动子区域特异性组蛋白掺入并抑制组蛋白乙酰化。我们在此报告，DNA 结合转录因子 Kruppel 样因子 5 (KLF5) 与新型组蛋白伴侣酸性核磷蛋白 32B (ANP32B) 相互作用，导致 KLF5 下游基因的转录抑制。我们进一步表明，将 ANP32B 招募到启动子区域需要 KLF5，并导致启动子区域特异性组蛋白掺入并通过 ANP32B 抑制组蛋白乙酰化。细胞外刺激（例如佛波酯）调节细胞中的这种机制。总的来说，我们鉴定了一种新的组蛋白伴侣 ANP32B，并通过对该因子的作用分析显示了一种在染色质水平上启动子区域特异性转录调控的新机制，该机制是由组蛋白伴侣和 DNA 结合转录因子之间的功能相互作用介导的。
Regulation of chromatin in eukaryotic transcription requires histone-modifying enzymes, nucleosome remodeling complexes, and histone chaperones. Specific regulation of histone incorporation/eviction by histone chaperones on the promoter (e.g., region specific) is still poorly understood. In the present study, we show that direct and functional interaction of histone chaperone and DNA-binding transcription factor leads to promoter region-specific histone incorporation and inhibition of histone acetylation. We report here that the DNA-binding transcription factor Kruppel-like factor 5 (KLF5) interacts with the novel histone chaperone acidic nuclear phosphoprotein 32B (ANP32B), leading to transcriptional repression of a KLF5-downstream gene. We further show that recruitment of ANP32B onto the promoter region requires KLF5 and results in promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B. Extracellular stimulus (e.g., phorbol ester) regulates this mechanism in the cell. Collectively, we have identified a novel histone chaperone, ANP32B, and through analysis of the actions of this factor show a new mechanism of promoter region-specific transcriptional regulation at the chromatin level as mediated by the functional interaction between histone chaperone and DNA-binding transcription factor.