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Differential regulation of the Sir2 histone
Research Article
Differential regulation of the Sir2 histone deacetylase gene
family by inhibitors of class I and II histone deacetylases
S. Kyrylenko a, O. Kyrylenko a, T. Suuronen a and A. Salminen b,*
a Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, 70211 Kuopio (Finland)
b Department of Neurology, University Hospital of Kuopio, P.O. Box 1777, 70211 Kuopio (Finland),
e-mail: antero.salminen@uku.fi
Received 28 February 2003; received after revision 19 June 2003; accepted 24 June 2003
Abstract. The Sir2 histone deacetylase gene family con-
sists of seven mammalian sirtuins (SIRTs) which are
NAD-dependent histone/protein deacetylases. Sir2 pro-
teins regulate, for instance, genome stability by chro-
matin silencing in yeast. In mammals, their function is
still largely unknown. Due to the NAD+ dependency, Sir2
might be the link between metabolic activity and his-
tone/protein acetylation. Regulation of gene expression
also seems to play an important role in Sir2 functions,
since increasing the dosage of Sir2 genes increases
genome stability in yeast and Caenorhabditis elegans.
We observed that the modification of histone/protein
acetylation status by several class I and II histone
deacetylase (HDAC) inhibitors induces differential
changes in gene expression profiles of seven SIRT mR-
NAs in cultured neuronal cells. SIRT2, SIRT4 and SIRT7
were upregulated, whereas SIRT1, SIRT5 and SIRT6
CMLS, Cell. Mol. Life Sci. 60 (2003) 1990–1997
1420-682X/03/091990-08
DOI 10.1007/s00018-003-3090-z
? Birkh?user Verlag, Basel, 2003
CMLS Cellular and Molecular Life Sciences
were downregulated by trichostatin A (TSA) and n-bu-
tyrate. The upregulation of SIRT mRNAs was inhibited
by actinomycin D. Interestingly, the regulation of SIRT
mRNAs was highly similar both in mouse Neuro-2a neu-
roblastoma cells and post-mitotic rat primary hippocam-
pal and cerebellar granule neurons. Using a chromatin
immunoprecipitation technique, we showed that the up-
regul
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