Regulation of nuclear histone acetyltransferase by nucleic acids, histone.DNA complex, and chromatin

Nuclear histone acetyltransferase is found to be inhibited by various nucleic acids and components. Of the adenosine phosphates, the order of inhibitory potency is ATP greater than ADP greater than AMP. Among the nucleoside triphosphates, GTP seems to be the best inhibitor, followed by ATP, CTP, and UTP. Deoxymononucleotides have the same order of inhibition potential as their ribonucleotide counterparts, with inhibition constants in the low millimolar range. Oligonucleotides and polynucleotides are much better inhibitors than mononucleotides. The inhibition constants of the DNA molecules are size dependent. Molecules larger than 40 base pairs have inhibition constants less than 18 micrograms/ml, whereas molecules with decreasing numbers of base pairs have increasing magnitudes of inhibition constants. However, acetyltransferase has a lower affinity for free DNA molecules than for DNA.histone complexes as revealed by its interaction with DNA-Sepharose and histone.DNA-Sepharose columns. Furthermore, native chromatin depleted of endogenous histone acetyltransferase activity shows no inhibitory effect on the enzyme. Yet heated chromatin not only loses substrate activity but also becomes an inhibitor for the enzyme. Since unmodified sea urchin sperm chromatin has been shown to be a potent acetyltransferase inhibitor, it seems possible that DNA.histone complexes may be the true inhibitory species and that the conformational states of such complexes may serve as a regulatory mechanism in the control of the enzyme activity.