Nucleic Acids Research, Vol 27, Issue 16 3355-3363, Copyright © 1999 by Oxford University Press
A Gunjan and DT Brown
BALB/c 3T3 cell lines containing integrated copies of the MMTV promoter
driving a reporter gene were constructed. Expression vectors in which
either of two H1 variants, H10 or H1c, were under control of an inducible
promoter were introduced into these lines. Surprisingly, overproduction of
either variant resulted in a dramatic increase in basal and hormone-induced
expression from the MMTV promoter. H1 overproduction also slowed the loss
of MMTV promoter activity associated with prolonged hormone treatment.
Transiently transfected MMTV reporter genes, which do not adopt a phased
nucleosomal arrangement, do not display increased activity upon H1
overproduction. Thus the effects observed for stable constructs most likely
represents a direct effect of H1 on a chromatin-mediated process specific
to the nucleosomal structure of the integrated constructs. Induction of
increased levels of acetylated core histones by treatment with trichostatin
A also potentiated MMTV activity and this effect was additive to that
caused by H1 overproduction. However, the effects of TSA treatment, in
control or H1-overproducing cells, were eliminated by inhibiting protein
synthesis. TSA treatment does not necessarily potentiate MMTV promoter
activity by increasing core histone acetylation within the MMTV promoter
but perhaps by altering the synthesis of an unlinked transcriptional
regulator.
ARTICLES
Overproduction of histone H1 variants in vivo increases basal and induced activity of the mouse mammary tumor virus promoter
Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
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