Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, 316 Ruth Leverton Hall, Lincoln, NE 68583-0806, USA.
Mutat Res. 2012 May 1;733(1-2):58-60. doi: 10.1016/j.mrfmmm.2011.08.001. Epub 2011 Aug 17.
Biotin serves as a covalently bound coenzyme in five human carboxylases; biotin is also attached to histones H2A, H3, and H4, although the abundance of biotinylated histones is low. Biotinylation of both carboxylases and histones is catalyzed by holocarboxylase synthetase. Human biotin requirements are unknown. Recommendations for adequate intake of biotin are based on the typical intake of biotin in an apparently healthy population, which is only a crude estimate of the true intake due to analytical problems. Importantly, intake recommendations do not take into account possible effects of biotin deficiency on impairing genome stability. Recent studies suggest that biotin deficiency causes de-repression of long terminal repeats, thereby causing genome instability. While it was originally proposed that these effects are caused by loss of biotinylated histones, more recent evidence suggests a more immediate role of holocarboxylase synthetase in forming multiprotein complexes in chromatin that are important for gene repression. Holocarboxylase synthetase appears to interact physically with the methyl-CpG-binding domain protein 2 and, perhaps, histone methyl transferases, thereby creating epigenetic synergies between biotinylation and methylation events. These observations might offer a mechanistic explanation for some of the birth defects seen in biotin-deficient animal models.
生物素在人体中的五种羧化酶中作为共价结合的辅酶；生物素也附着在组蛋白 H2A、H3 和 H4 上，尽管生物素化组蛋白的丰度较低。羧化酶和组蛋白的生物素化均由全羧化酶合成酶催化。人体对生物素的需求尚不清楚。生物素充足摄入量的建议是基于在看似健康的人群中生物素的典型摄入量，由于分析问题，这只是对真实摄入量的粗略估计。重要的是，摄入量建议并没有考虑生物素缺乏对损害基因组稳定性的可能影响。最近的研究表明，生物素缺乏会导致长末端重复序列去抑制，从而导致基因组不稳定。虽然最初提出这些影响是由于生物素化组蛋白的丢失所致，但最近的证据表明，全羧化酶合成酶在形成染色质中对于基因抑制很重要的多蛋白复合物中具有更直接的作用。全羧化酶合成酶似乎与甲基-CpG 结合域蛋白 2 物理相互作用，并且可能与组蛋白甲基转移酶相互作用，从而在生物素化和甲基化事件之间产生表观遗传协同作用。这些观察结果可能为生物素缺乏动物模型中观察到的一些出生缺陷提供机制解释。
