Toward a Biology Worthy of Life > Getting Over the Code Delusion > Brief excerpt
A project by Stephen L. Talbott

The language of histone tail modifications

After a few histone tail modifications were found to be rather distinctly associated with active or repressed genes, the forlorn hope arose that we would discover a precise, combinatorial “histone code”. It would provide a fixed and reliable key enabling us to predict the consequences of any arrangement of modifications.

But this was to ignore the nearly infinite variety of all those contextual factors that blend their voices in concert with the histone modifications. In the plastic organism, what goes on at the local level is always shaped and guided by a larger, coherent context — a context that surely has meaning, but (as in all natural languages) never an absolutely fixed grammar. And, in fact, while overwhelming evidence for a meaningful, gene-regulatory conversation involving histone modifications has emerged, there is little to suggest a rigid code. Shelley Berger of Philadelphia’s Wistar Institute, noting that a single tail modification “recruits numerous proteins whose regulatory functions are not only activating but also repressing” and that “many of these marks have several, seemingly conflicting roles”, summarized the situation this way:

Although [histone] modifications were initially thought to be a simple code, a more likely model is of a sophisticated, nuanced chromatin “language” in which different combinations of basic building blocks yield dynamic functional outcomes.
Berger further envisions histone modifications as participating in “an intricate ‘dance’ of associations”.

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