The inhibitory effects of calf thymus-histone fractions on the development of the chick embryo.

The genetic potentialities of an egg are transcribed, translated and built up into a temporal-spatial organization by epigenetic processes. How are these potentialities realized? Efforts to answer this question have naturally turned towards a study of the activity of the genetic material, which according to modern ideas is entirely composed of DNA. Stedmann & Stedmann (1950) originally suggested that certain basic proteins (histones) present in the nucleus were gene inhibitors. Since then various biochemical aspects of histone metabolism have been studied (see review by Phillips, 1962). A number of distinct histones have been isolated (Butler, 1964). But tissues from different species of animals or different tissues from the same species have been found to possess very similar complements of histones (Hnilica, Johns & Butler, 1962). No specificity of interaction between histones and different parts of the DNA molecule has been observed (Johns & Butler, 1964). However, histones have been found to inhibit the synthesis of DNA-dependent RNA (Huang & Bonner, 1962; Barr & Butler, 1963; Allfrey, Littau & Mirsky, 1963; Bonner & Huang, 1964). Changes in staining properties and distribution of DNA-associated basic proteins have been shown to accompany early developmental processes (Bloch, 1962; Bloch & Hew, 1960; Moore, 1963; Horn, 1962; Das, Kaufmann & Gay, 1964 a, b). Such changes indicate a possible significant role of histones in differentiation. A study of the effects of extraneous histones on embryonic development could be expected to provide some evidence on this point. If histones are gene inhibitors, specific fractions might show inhibition of specific organ systems or at least a well-defined pattern of inhibition.