Histone demethylase LSD1 is a folate-binding protein.
Histone demethylase LSD1 is a folate-binding protein.
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DOI：
10.1021/bi200247b
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发表时间：
2011-05-31
期刊：
影响因子：
2.9
通讯作者：
Wagner C
中科院分区：
文献类型：
--
作者：
Luka Z;Moss F;Loukachevitch LV;Bornhop DJ;Wagner C
已知组蛋白中赖氨酸残基的甲基化在基因表达中发挥调节作用。尽管早在 1973 年就发现了酶法去除甲基的方法，但负责去除甲基的酶却被分离出来，并且直到最近才描述了它们的作用机制。第一个显示出这种活性的酶是 LSD1，这是一种含有黄素的酶，可以去除组蛋白 3 的 4 号和 9 号赖氨酸上的甲基，同时从甲基上生成甲醛。该反应类似于先前描述的由二甲基甘氨酸脱氢酶和肌氨酸脱氢酶进行的去甲基化反应，其中蛋白质结合的四氢叶酸充当所产生的甲醛的受体。我们现在证明 HeLa 细胞的核提取物含有与叶酸相关的 LSD1。使用背向散射干涉测量 (BSI) 方法，我们测量了游离溶液中各种形式的叶酸与全长 LSD1 和截短形式的 LSD1 的结合。四氢叶酸天然五谷氨酸形式的 (R,S) 形式与全长 LSD1 的结合力最高 (Kd = 2.8 µM)。叶酸参与组蛋白的酶促去甲基化这一事实为这种微量营养素在基因表达的表观遗传控制中发挥作用提供了机会。
Methylation of lysine residues in histones has been known to serve a regulatory role in gene expression. Although enzymatic removal of the methyl groups was discovered as early as 1973 the enzymes responsible for their removal were isolated and their mechanism of action was described only recently. The first enzyme to show such activity was LSD1, a flavin containing enzyme that removes the methyl groups from lysines 4 and 9 of histone 3 with the generation of formaldehyde from the methyl group. This reaction is similar to the previously described demethylation reactions carried out by the enzymes dimethylglycine dehydrogenase and sarcosine dehydrogenase, in which protein-bound tetrahydrofolate serves as an accepter of the formaldehyde that is generated. We now show that nuclear extracts of HeLa cells contain LSD1 that is associated with folate. Using the method of Back-Scattering Interferometry (BSI) we have measured the binding of various forms of folate to both full length LSD1 and to a truncated form of LSD1 in free solution. The (R,S) form of the natural pentaglutamate form of tetrahydrofolate bound with the highest affinity (Kd = 2.8 µM) to full length LSD1. The fact that folate participates in the enzymatic demethylation of histones provides an opportunity for this micronutrient to play a role in the epigenetic control of gene expression.
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影响因子：
3.5
作者：
Forneris, F;Binda, C;Battaglioli, E
通讯作者：
Battaglioli, E
影响因子：
64.8
作者：
BLAKLEY, RL
通讯作者：
BLAKLEY, RL
影响因子：
3.9
作者：
Walkup, AS;Appling, DR
通讯作者：
Appling, DR
影响因子：
6.8
作者：
Anderson, Donald D.;Woeller, Collynn F.;Stover, Patrick J.
通讯作者：
Stover, Patrick J.
DOI：
10.1073/pnas.77.8.4484
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
WITTWER, AJ;WAGNER, C
通讯作者：
WAGNER, C