Selective regulation of class I and class II histone deacetylases expression by inhibitors of histone deacetylases in cultured mouse neural cells.
The expression of 10 histone deacetylases (HDAC1-10) mRNAs in mouse neuroblastoma Neuro-2a and microglia N9 cell cultures after treatment by inhibitors of HDACs, sodium butyrate and trichostatin A was studied to elucidate whether HDAC inhibitors affect the gene expression of HDACs themselves. Northern blot analysis demonstrated two- to four-fold elevated levels of mRNAs for HDAC1, -3, -5, and -6 after drug treatment in comparison with untreated cells, while mRNA levels for HDAC2 and -7 did not change significantly. In both Neuro-2a and N9 cells the highest increase was observed for HDAC5 and -6 mRNA, whereas, HDAC4 had a prominent increase in mRNA levels after drug treatment only in N9 microglia cell line but not in Neuro-2a. Immunocytochemical examination confirmed that changes in protein levels of HDACs were similar to changes in their mRNA levels. There exists an auto-regulatory feedback loop to the expression levels of several HDACs after inhibition of their biochemical activity, adding several HDAC genes to the list of genes regulated by HDAC inhibitors.
Ajamian
Farzam
F
Department of Neurobiology, A.I. Virtanen Institute for Molecular Science, University of Kuopio, P.O. Box 1627 (Neulaniementie 2), FIN 70211 Kuopio, Finland.
Salminen
Antero
A
Reeben
Mati
M
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics
D004791:Enzyme Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C484389:Hdac1 protein, mouse; C533424:Hdac2 protein, mouse; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases