Novel histone biotinylation marks are enriched in repeat regions and participate in repression of transcriptionally competent genes.
Novel histone biotinylation marks are enriched in repeat regions and participate in repression of transcriptionally competent genes.
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新型的组蛋白生物素化标记富集在重复区域，并参与转录竞争基因的抑制。
DOI：
10.1016/j.jnutbio.2010.02.011
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发表时间：
2011-04
影响因子：
5.6
通讯作者：
Zempleni, Janos
中科院分区：
文献类型：
--
作者：
Pestinger, Valerie;Wijeratne, Subhashinee S. K.;Rodriguez-Melendez, Rocio;Zempleni, Janos
组蛋白共价修饰在染色质结构和基因组稳定性中起着至关重要的作用。我们先前报道了全羧化酶合成酶对组蛋白H2 A、H3和H4中赖氨酸（K）残基的生物素化，并证明了K12-生物素化组蛋白H4（H4 K12 bio）富集在重复区域并参与基因阻遏。除了H4 K12 bio之外，生物素化标记的生物学功能知之甚少。在这里，针对H3 K9 bio、H3 K18 bio和H4 K8 bio的新型生物素化位点特异性抗体被用于染色质免疫沉淀研究，以首次了解这些标记的可能生物学功能。在人原代成纤维细胞和Jurkat淋巴母细胞瘤细胞中进行染色质免疫沉淀测定，并揭示H3 K9 bio、H3 K18 bio和H4 K8 bio富含重复区域，如着丝粒周围α卫星重复和长末端重复，同时耗尽常染色质中的转录活性启动子。抑制的白细胞介素-2启动子的转录刺激触发了Jurkat细胞中该位点的组蛋白生物素化标记的快速耗尽，这被白细胞介素-2 mRNA的增加所抑制。重要的是，H3 K9 bio、H3 K18 bio和H4 K8 bio在基因组位点的富集依赖于培养基中营养相关水平的生物素浓度，这表明生物素调控基因的新机制。
Covalent histone modifications play crucial roles in chromatin structure and genome stability. We previously reported biotinylation of lysine (K) residues in histones H2A, H3, and H4 by holocarboxylase synthetase, and demonstrated that K12-biotinylated histone H4 (H4K12bio) is enriched in repeat regions and participates in gene repression. The biological functions of biotinylation marks other than H4K12bio are poorly understood. Here, novel biotinylation site-specific antibodies against H3K9bio, H3K18bio, and H4K8bio were used in chromatin immunoprecipitation studies to obtain first insights into possible biological functions of these marks. Chromatin immunoprecipitation assays were conducted in human primary fibroblasts and Jurkat lymphoblastoma cells, and revealed that H3K9bio, H3K18bio, and H4K8bio are enriched in repeat regions such as pericentromeric alpha satellite repeats and long-terminal repeats while being depleted in transcriptionally active promoters in euchromatin. Transcriptional stimulation of the repressed interleukin-2 promoter triggered a rapid depletion of histone biotinylation marks at this locus in Jurkat cells, which was paralleled by an increase in interleukin-2 mRNA. Importantly, the enrichment of H3K9bio, H3K18bio, and H4K8bio at genomic loci depended on the concentration of biotin in culture media at nutritionally relevant levels, suggesting a novel mechanism of gene regulation by biotin.
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