The isolation of HTC variant cells which can replicate in butyrate. Changes in histone acetylation and tyrosine aminotransferase induction.
We have obtained a number of variant HTC cells which are capable of vigorous replication in the presence of 6 mM sodium butyrate. These cells show characteristic changes in histone acetylation. H2A/H2B are no longer modified and the turnover of histones H3/H4 acetate is about 4-fold greater than in control HTC cells at the same butyrate concentration. Histone deposition continues successfully even though histones H3/H4 become hyperacetylated upon association with the chromatin. Prompt deacetylation of new histones does not appear to be a prerequisite for successful deposition processes. Initial enzymatic studies indicate that not only do the butyrate-resistant cells show an increased deacetylase activity (on a per cell basis), but also the enzyme is less sensitive to sodium butyrate under in vitro assay conditions. In contrast to control HTC cells in 6 mM butyrate in which dexamethasone induction of tyrosine aminotransferase is inhibited, the butyrate-resistant variant cells are capable of tyrosine aminotransferase induction even in the presence of butyrate. The implications of these observations are discussed.
Chalkley
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R
Shires
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D000107:Acetylation; D000818:Animals; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D004351:Drug Resistance; D004790:Enzyme Induction; D014644:Genetic Variation; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D002087:Butyrates; D006657:Histones; D020148:Butyric Acid; D003907:Dexamethasone; D014444:Tyrosine Transaminase; D006655:Histone Deacetylases