Enzymic modification of chromosomal macromolecules: III. The effect of adenine nucleotides on histone modification in chromatin and a possible influence of steroid hormones

Abstract

Although adenosine 3′,5′-monophosphate (cyclic AMP) had no effect on the methylation of histone lysine residues as catalysed by chromatin of Krebs 2 ascites tumour cells, AMP was found to be stimulatory. With a soluble histone-free preparation extracted from the particulate chromatin as source of histone methylase the stimulatory effect of AMP was still observable but much less marked. Histone kinase activity was also detectable in both intact chromatin and the soluble preparation but surprisingly cyclic AMP had only a meagre stimulatory effect, and AMP was somewhat inhibitory. Nevertheless cyclic AMP had a pronounced stimulatory effect on histone phosphorylation catalysed by a soluble preparation from whole cell homogenates. On the other hand whilst histone acetylase activity was observable in chromatin, neither cyclic AMP nor AMP had any effect. A potential means of regulating the levels of AMP and cyclic AMP within chromatin was also demonstrable in the shape of the chromatin enzyme activities, adenyl cyclase and cyclic AMP phosphodiesterase. Of these activities the latter was markedly inhibited by a spectrum of steroid hormones.