M. Chireux et al., HISTONE HYPERACETYLATING AGENTS STIMULATE PROMOTER ACTIVITY OF HUMAN CHOLINE-ACETYLTRANSFERASE GENE IN TRANSFECTION EXPERIMENT, Molecular brain research, 39(1-2), 1996, pp. 68-78
Butyrate (5 mM), Trichostatin A (1 mu M) or Trapoxin A (30 nM) increas
ed choline acetyltransferase (ChAT) activity in cultured rat sympathet
ic neurons 3- to 8-fold in 2 days. On the contrary, the three drugs de
creased ChAT activity in human CHP126 cells. Butyrate had little effec
t on ChAT mRNA level in these cells, suggesting post-transcriptional m
echanisms for the decrease in ChAT activity. However, transient transf
ection experiments using CHP126 cells revealed that the M promoter, bu
t not the R promoter, of human ChAT gene was activated 20- to 130-fold
by the three hyperacetylating agents. A butyrate-responsive element w
as localized in the 1 kbp region upstream of exon M. Constructs contai
ning in addition the genomic segment between exons M and 1 displayed m
aximal basal activity and inducibility by butyrate, suggesting the pre
sence of butyrate-activated promoter/enhancer elements in this region.
The stimulatory effects of butyrate and Trichostatin A were also obse
rved in stably transfected CHP126 clones, suggesting that the chromati
n environment was not preventing the induction of the endogenous ChAT
gene by butyrate, Rather, the data suggest different chromatin organiz
ations for the stable transgene and the endogenous ChAT gene.