剪接调节NAD代谢物与组蛋白macroH2A的结合。
Splicing regulates NAD metabolite binding to histone macroH2A.
作者信息
Kustatscher Georg, Hothorn Michael, Pugieux Céline, Scheffzek Klaus, Ladurner Andreas G
机构信息
Gene Expression Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
出版信息
Nat Struct Mol Biol. 2005 Jul;12(7):624-5. doi: 10.1038/nsmb956. Epub 2005 Jun 19.
Histone macroH2A is a hallmark of mammalian heterochromatin. Here we show that human macroH2A1.1 binds the SirT1-metabolite O-acetyl-ADP-ribose (OAADPR) through its macro domain. The 1.6-A crystal structure and mutants reveal how the metabolite is recognized. Mutually exclusive exon use in the gene H2AFY produces macroH2A1.2, whose tissue distribution differs. MacroH2A1.2 shows only subtle structural changes but cannot bind nucleotides. Alternative splicing may thus regulate the binding of nicotinamide adenine dinucleotide (NAD) metabolites to chromatin.
组蛋白巨H2A是哺乳动物异染色质的一个标志。我们在此表明，人类巨H2A1.1通过其巨结构域结合SirT1代谢物O-乙酰-ADP-核糖（OAADPR）。1.6埃的晶体结构及突变体揭示了该代谢物的识别方式。基因H2AFY中相互排斥的外显子使用产生了巨H2A1.2，其组织分布有所不同。巨H2A1.2仅显示出细微的结构变化，但无法结合核苷酸。因此，可变剪接可能调控烟酰胺腺嘌呤二核苷酸（NAD）代谢物与染色质的结合。
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