We revisit the notion of gene regulatory code in embryonic development in the
light of recent findings about genome spatial organisation. By analogy with the
genetic code, we posit that the concept of code can only be used if the
corresponding adaptor can clearly be identified. An adaptor is here defined as
an intermediary physical entity mediating the correspondence between codewords
and objects in a gratuitous and evolvable way. In the context of the gene
regulatory code, the encoded objects are the gene expression levels, while the
concentrations of specific transcription factors in the cell nucleus provide
the codewords. The notion of code is meaningful in the absence of direct
physicochemical relationships between the objects and the codewords, when the
mediation by an adaptor is required. We propose that a plausible adaptor for
this code is the gene domain, that is, the genome segment delimited by
topological insulators and comprising the gene and its enhancer regulatory
sequences. We review recent evidences, based on genome-wide chromosome
conformation capture experiments, showing that preferential contact domains
found in metazoan genomes are the physical traces of gene domains. Accordingly,
genome 3D folding plays a direct role in shaping the developmental gene
regulatory code.
arXiv Quantitative Biology
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