Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate (Science, 2009, 325:1254-1257)

報告日期: 2010/05/18
報告時間: 17:10/18:00
報告學生: 湯硯安
講評老師: 林秋烽
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990518-1.pdf

Regulation of Histone Acetylation in the Nucleus by Sphingosine-1-Phosphate

 

Hait, N.C., Allegood, J., Maceyka, M., Strub, G.M., Harikumar, K.B., Singh, S.K., Luo, C., Marmorstein, R., Kordula, T., Milstien, S., and Spiegel, S.

Science, 325: 1254–1257, 2009

 

Speaker: Yen-An Tang (湯硯安)

Commentator: Dr. Chiou-Feng Lin (林秋烽教授)

Date: 2010/05/18 (pm 17:10-18:00)

Room: 602

 

Abstract:

Phospholipid metabolites have been shown to function as signal messengers that relay many cellular signal cascades. The sphingosine-1-phosphate (S1P), a sphingolipid metabolite, is an important player in regulation of cellular and physiological processes, including cell growth, movement, angiogenesis and immunity in a receptor-dependent or independent manner. S1P is generated by two closely related shpingosine kinases, SphK1 and SphK2. Much has been learned about SphK1, whereas the functions of SphK2 remain unclear. Since SphK2 is mainly localized to the nucleus, it is worthy to explore its function in relation to S1P, whose nuclear function also has not been identified.

The author showed that SphK2 was enriched in the chromatin fraction, where it specifically bound to histone H3. Ectopic expression of SphK2 or treatment with S1P increased acetylation of histone H3, H4 and H2B. In contrast, knockdown of SphK2 resulted in decreases in histone acetylation, which was restored by either overexpression of non-siRNA-targeted SphK2 or treatment with S1P. This phenomenon was due to the blockage of histone deacetylase (HDAC) activity of HDAC1/2 by S1P via direct binding to the catalytic domain of them. Moreover, SphK2 was associated with the promoter of p21 and c-fos genes, and triggered local histone H3 acetylation and thus enhanced gene transcription. This study demonstrates promising evidences that nuclear S1P functions as endogenous HDAC inhibitor and links lipid metabolism to epigenetic regulation of gene expression.

 

Reference:

1.    Spiegel, S., Milstien, S. 2007. Functions of the multifaceted family of sphingosine kinases and some close relatives. J Biol Chem. 282, 2125–2129.

2.    Hait, N.C., Allegood, J., Maceyka, M., Strub, G.M., Harikumar, K.B., Singh, S.K., Luo, C., Marmorstein, R., Kordula, T., Milstien, S., and Spiegel, S. 2009. Regulation of histone acetylation in the nucleus by sphingosine-1-phosphate. Science, 325: 1254–1257. this issue.