J Comput Biol 2019 Jul 01;267:685-695. doi: 10.1089/cmb.2019.0097.

How Does the Regulatory Genome Work?

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The regulatory genome controls genome activity throughout the life of an organism. This requires that complex information processing functions are encoded in, and operated by, the regulatory genome. Although much remains to be learned about how the regulatory genome works, we here discuss two cases where regulatory functions have been experimentally dissected in great detail and at the systems level, and formalized by computational logic models. Both examples derive from the sea urchin embryo, but assess two distinct organizational levels of genomic information processing. The first example shows how the regulatory system of a single gene, endo16, executes logic operations through individual transcription factor binding sites and cis-regulatory modules that control the expression of this gene. The second example shows information processing at the gene regulatory network (GRN) level. The GRN controlling development of the sea urchin endomesoderm has been experimentally explored at an almost complete level. A Boolean logic model of this GRN suggests that the modular logic functions encoded at the single-gene level show compositionality and suffice to account for integrated function at the network level. We discuss these examples both from a biological-experimental point of view and from a computer science-informational point of view, as both illuminate principles of how the regulatory genome works.

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Genes referenced: endo16 LOC100887844 LOC115926321 LOC575170

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