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Published July 2019 | Published
Journal Article Open

How Does the Regulatory Genome Work?


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.

Additional Information

© 2019, Mary Ann Liebert, Inc. In memory of Eric Davidson, who 50 years ago envisioned the importance of gene regulation and who together with Roy Britten built a theoretical foundation ("Gene regulation for higher cells: a theory" Science, 1969), many years before the regulatory genome became accessible to experimental exploration in animals. We are grateful to Deanna Thomas for her help in generating the figures. This work was supported by National Institutes of Health Grant HD 037105 (to I.S.P.). The authors declare there are no competing financial interests.

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