Histone redistribution and conformational effect on chromatin induced by formaldehyde

Abstract

Histone redistributions between endogenous DNA in calf thymus chromatin and exogenous DNA from Clostridium perfringens (69% A + T) or from Micrococcus luteus (30% A + T) induced by 0.6 M NaCl or by 2% formaldehyde were studied by thermal denaturation. The observed redistribution occurred on histone Hl when the exogenous DNA was (A + T)-richer than the DNA in chromatin, and when the mixture was exposed to 0.6 M NaCl or formaldehyde. When a (G + C)-richer DNA was added as the acceptor for histones, no substantial transfer of histones from chromatin DNA to exogenous DNA was found. Thus the activation energy of histone dissociation from chromatin DNA seems to be substantially lowered by 0.6 M NaCl or formaldehyde such that histones (mostly histone Hl) can be dissociated and bind the (A + T)-richer DNA and form a more stable complex. It is suggested that the formaldehyde effect on histones may be due to the loss of positive charges on lysine and arginin residues (probably more on lysine than on arginine) in histones after their rapid reaction with formaldehyde. Formaldehyde treatment of chromatin also distorts the DNA conformation, as revealed by circular dichroism (CD) studies. This structural effect occurs mainly on those base pairs bound by histones other than Hl, or within the chromatin subunit. Histone redistribution is treated as a thermodynamic phenomenon of histone binding to DNA. The validity of using formaldehyde to study chromatin structure is discussed.