The epigenetic code: The link between chromatin structure & function during development
It is now clearly established that the central regulator of eukaryotic gene transcription is the organisation of the genome into chromatin. Chromatin performs this crucial function by partitioning the genome into domains that are either open and transcriptionally active or closed and repressed. Chromatin is built from nucleosomes (histones plus DNA), the universal repeating protein-DNA complex in all eukaryotic cells. Significantly, the tail of each histone protrudes on the outside of the nucleosome and is subject to an extensive range of enzyme-catalysed modifications of site-specific amino acid residues in response to intrinsic and external signals. Functionally, it has been argued that the combination of such modifications is recognised or read by specific chromatin binding proteins involved in regulating transcription and/or chromatin structure. However, our recent work has shown that the functional readout of specific histone modifications is not sufficient to control chromatin function but is also dependent upon the composition of the underlying nucleosome. Studies are aimed at elucidating how the composition of the nucleosome changes to regulate cellular differentiation.