Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate.
Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate.
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DOI：
10.1126/science.1176709
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发表时间：
2009-09-04
期刊：
影响因子：
--
通讯作者：
Spiegel S
中科院分区：
文献类型：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
多效性脂质介质1 -磷酸鞘氨醇（S1P）可通过未知机制在细胞内独立于其细胞表面受体发挥作用。鞘氨醇激酶2（SphK2）是产生S1P的同工酶之一，它与组蛋白H3相关联并产生调节组蛋白乙酰化的S1P。S1P特异性结合组蛋白去乙酰化酶HDAC1和HDAC2并抑制其酶活性，防止从组蛋白尾部的赖氨酸残基上去除乙酰基。SphK2在阻遏复合物中与HDAC1和HDAC2相关联，并在编码细胞周期蛋白依赖性激酶抑制剂p21或转录调节因子c - fos的基因启动子处选择性富集，在那里它增强局部组蛋白H3乙酰化和转录。因此，HDAC是S1P的直接细胞内靶点，并将核内S1P与基因表达的表观遗传调控联系起来。
The pleiotropic lipid mediator sphingosine-1-phosphate (S1P) can act intracellularly independently of its cell surface receptors through unknown mechanisms. Sphingosine kinase 2 (SphK2), one of the isoenzymes that generates S1P, was associated with histone H3 and produced S1P that regulated histone acetylation. S1P specifically bound to the histone deacetylases HDAC1 and HDAC2 and inhibited their enzymatic activity, preventing the removal of acetyl groups from lysine residues within histone tails. SphK2 associated with HDAC1 and HDAC2 in repressor complexes and was selectively enriched at the promoters of the genes encoding the cyclin-dependent kinase inhibitor p21 or the transcriptional regulator c-fos, where it enhanced local histone H3 acetylation and transcription. Thus, HDACs are direct intracellular targets of S1P and link nuclear S1P to epigenetic regulation of gene expression.
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影响因子：
11.2
作者：
Sankala, Heidi M.;Hait, Nitai C.;Spiegel, Sarah
通讯作者：
Spiegel, Sarah
影响因子：
64.8
作者：
Finnin, MS;Donigian, JR;Pavletich, NP
通讯作者：
Pavletich, NP
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Ding, Guo;Sonoda, Hirofumi;Nakamura, Shun-ichi
通讯作者：
Nakamura, Shun-ichi
影响因子：
4.1
作者：
Albi, Elisabetta;Lazzarini, Remo;Magni, Mariapia Viola
通讯作者：
Magni, Mariapia Viola