Overproduction of histone H1 variants in vivo increases basal and induced activity of the mouse mammary tumor virus promoter

BALB/c 3T3 cell lines containing integrated copies of the MMTV promoter dri ving a reporter gene were constructed. Expression vectors in which either o f two H1 variants, H1(0) or H1c, were under control of an inducible promote r were introduced into these lines, Surprisingly, overproduction of either variant resulted in a dramatic increase in basal and hormone-induced expres sion 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 a rrangement, 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 st ructure of the integrated constructs. Induction of increased levels of acet ylated 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 ISA treatment, in control or H1-overproducing cell s, were eliminated by inhibiting protein synthesis. TSA treatment does not necessarily potentiate MMTV promoter activity by increasing core histone ac etylation within the MMTV promoter but perhaps by altering the synthesis of an unlinked transcriptional regulator.