Commentary: The information of conformation

In the 1870s, intensive microscopical work to analyse the dynamics of cell division produced a new entity for the cell: chromatin, so named by Walter Flemming because it readily took up histological dyes. The word means coloured substance. Thus it is a rather arbitrary word, more to do with the technique of visualization than a descriptor of the thing. Nonetheless, before the ascendance of the gene concept, the powers of heredity were ascribed to chromatin. As EB Wilson put it in 1900, chromatin ‘seems to have the power to produce all the other elements’ of the nucleus. With the rise of the gene in the 20th century, chromosomes were seen as gene-carriers; with the identification of DNA as the hereditary material, the importance of ‘chromatin as the physical basis of inheritance’—as it was frequently described in the first half of the 20th century—receded still further. This conceptual separation between DNA as the locus of information and its transmission, and chromatin as a mere scaffold was as arbitrary as the initial naming of chromatin: after all, chromatin is, by definition, the complex of DNA and proteins constituting the contents of the nucleus (and one wonders today if the definition of chromatin should not include RNA). A key point of Jablonka and Lamb’s now classic ‘The inheritance of acquired epigenetic variations’ is to insist that DNA never comes alone: chromatin structure and conformation are redescribed as ‘the gene’s phenotype’. Italicized in the original to draw attention to the importance and perhaps anti-intuitive nature of the phrase, chromatin is highlighted here as the animate body of the gene. For this reader, it is a description that evokes both ideas of chromatin before DNA—such as De Vries’ notion of chromatin as a living colony of invisible biophores—as well as the future that would come after 1989, a renaissance in chromatin biology. Today, the complex architecture and topography of chromatin, as well as its temporal dynamism, is at the centre of research in gene regulation and epigenetics. Chromatin has become an ‘integration and storage platform’ for signals coming into the cell, the ‘physiological template of all eukaryotic genetic information’, the nuclear ‘landscape’ of pluripotency and senescence and ‘the physiological form of our genome’. Indeed, if the 20th century was the century of the gene, as historian Evelyn Fox Keller puts it, the 21st may well turn out to be the century of chromatin. It is instructive, therefore, to return to the role of chromatin in this seminal theorization of epigenetic inheritance. Chromatin structure and conformation were proposed as the gene’s phenotype, that which ‘determines its functional state’. Evidence was offered from studies with nuclease enzymes, which were useful because they could only cut the DNA strand if the enzyme could get at it, implying an open conformation of chromatin. More important than the experimental evidence brought to bear on the question of chromatin conformation is the rhetorical construction of chromatin as an impressionable physical material. It was pliable enough to take the imprint of an environmental or developmental event, but stable enough to then hold that imprint beyond the time of the initial event and forward into subsequent generations, such that the change became ‘stimulus independent’. What, exactly, was theorized as being transmitted across cell generations in chromatin, including the meiotic divisions that produced germ cells and therefore carried these changes into later generations? The newly emergent study of methylation, enabled by DNA-cutting enzymes and other chemical