Impairment of histone H1 DNA binding by adduct formation with acetaldehyde.
Incubation of histone H1 with pharmacologically relevant concentrations of acetaldehyde resulted in the formation of spontaneously stable acetaldehyde-protein linkages. The reaction of acetaldehyde and H1 purified from rat liver either by a DNA recognition site affinity chromatography or by perchloric acid extraction occurred primarily at the lysine residues in the carboxyterminal tail of H1, which is crucial for its function as a eukaryotic repressor. It was further shown using an H1-lacZ fusion protein produced in E. coli and the protein isolated from rat liver that the formation of acetaldehyde adducts with H1 impair its DNA binding properties. We propose that such a reaction may occur in vivo and lead to an inability to repress genes in the liver upon excessive alcohol consumption. This mechanism may play a role in acetaldehyde-induced collagen synthesis in alcoholics.
Niemelä
O
O
Collagen Research Unit, University of Oulu, Finland.
Mannermaa
R M
RM
Oikarinen
J
J
D000079:Acetaldehyde / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002846:Chromatography, Affinity; D004268:DNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D006657:Histones / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D006657:Histones; D015345:Oligonucleotide Probes; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000079:Acetaldehyde; D008239:Lysine