K16-biotinylated histone H4 is overrepresented in repeat regions and participates in the repression of transcriptionally competent genes in human Jurkat lymphoid cells.
K16-biotinylated histone H4 is overrepresented in repeat regions and participates in the repression of transcriptionally competent genes in human Jurkat lymphoid cells.
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DOI：
10.1016/j.jnutbio.2011.10.009
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发表时间：
2012-12
影响因子：
5.6
通讯作者：
Zempleni, Janos
中科院分区：
文献类型：
--
作者：
Rios-Avila, Luisa;Pestinger, Valerie;Zempleni, Janos
全羧化酶合成酶（HCS）催化生物素与组蛋白H3和H4中的赖氨酸（K）残基的结合。组蛋白生物素化标记在阻遏基因座中富集，包括反转录转座子。初步研究表明，组蛋白H4中的K16是HCS生物素化的靶点。在这里，我们测试的假设，H4 K16 bio是一个真实的组蛋白标记在人类染色质，和H4 K16 bio是在阻遏基因位点和重复区域过度。产生多克隆兔抗人H4 K16 bio并亲和纯化。对合成和天然靶标进行的一系列广泛测试证实，这种新抗体对H4 K16 bio具有特异性。使用抗H4 K16 bio和染色质免疫沉淀分析，我们证明了H4 K16 bio在重复区域[近着丝粒α卫星重复序列和长末端重复序列（LTR）]中的比例高于常染色质启动子。H4 K16 bio也富含人类淋巴细胞中受抑制的白细胞介素-2基因启动子;有丝分裂原和佛波醇酯对白细胞介素-2基因的转录激活与基因启动子处H4 K16 bio标记的耗竭相吻合。H4 K16 bio的富集依赖于生物素的供应;与生物素正常和生物素缺乏的细胞相比，在补充生物素的细胞中，钠依赖性多种维生素转运蛋白（SMVT）的LTR 22和启动子1处的富集更大。与HCS野生型对照相比，H4 K16 bio在LTR 15和SMVT启动子1处的富集在来自HCS缺陷型患者的成纤维细胞中显著较低。我们的结论是，H4 K16生物是一个真实的现象，这个标志，像其他生物素标记，是过度的抑制基因座，它标志着HCS对接站点。
Holocarboxylase synthetase (HCS) catalyzes the binding of biotin to lysine (K) residues in histones H3 and H4. Histone biotinylation marks are enriched in repressed loci, including retrotransposons. Preliminary studies suggested that K16 in histone H4 is a target for biotinylation by HCS. Here we tested the hypotheses that H4K16bio is a real histone mark in human chromatin, and that H4K16bio is overrepresented in repressed gene loci and repeat regions. Polyclonal rabbit anti-human H4K16bio was generated and affinity purified. An extensive series of testing with synthetic and natural targets confirmed that this new antibody is specific for H4K16bio. Using anti-H4K16bio and chromatin immunoprecipitation assays, we demonstrated that H4K16bio is overrepresented in repeat regions [pericentromeric alpha satellite repeats and long terminal repeats (LTR)] compared with euchromatin promoters. H4K16bio was also enriched in the repressed interleukin-2 gene promoter in human lymphoid cells; transcriptional activation of the interleukin-2 gene by mitogens and phorbol esters coincided with a depletion of the H4K16bio mark at the gene promoter. The enrichment of H4K16bio depended on biotin supply; the enrichment at LTR22 and promoter 1 of the sodium-dependent multivitamin transporter (SMVT) was greater in biotin-supplemented cells compared with biotin-normal and biotin-deficient cells. The enrichment of H4K16bio at LTR15 and SMVT promoter 1 was significantly lower in fibroblasts from an HCS-deficient patient compared with an HCS wild-type control. We conclude that H4K16bio is a real phenomenon and that this mark, like other biotinylation marks, is overrepresented in repressed loci where it marks HCS docking sites.
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DOI：
10.1046/j.0014-2956.2001.02481.x
发表时间：
2001-10-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Stanley, JS;Griffin, JB;Zempleni, J
通讯作者：
Zempleni, J
影响因子：
14.8
作者：
Dahl, John Arne;Collas, Philippe
通讯作者：
Collas, Philippe
影响因子：
5.4
作者：
Kobza, K;Camporeale, G;Zempleni, J
通讯作者：
Zempleni, J
影响因子：
4.2
作者：
Manthey, KC;Griffin, JB;Zempleni, J
通讯作者：
Zempleni, J
影响因子：
2.9
作者：
Bailey, L. M.;Ivanov, R. A.;Polyak, S. W.
通讯作者：
Polyak, S. W.