Sequential Response to Multiple Developmental Network Circuits Encoded in an Intronic cis-Regulatory Module of Sea Urchin hox11/13b

Publication date: 11 April 2017
Source:Cell Reports, Volume 19, Issue 2
Author(s): Miao Cui, Erika Vielmas, Eric H. Davidson, Isabelle S. Peter
Gene expression in different spatial domains is often controlled by separate cis-regulatory modules (CRMs), but regulatory states determining CRM activity are not only distinct in space, they also change continuously during developmental time. Here, we systematically analyzed the regulatory sequences controlling hox11/13b expression and identified a single CRM required throughout embryonic gut development. We show that within this CRM, distinct sets of binding sites recognizing Ets, Tcf, and homeodomain transcription factors control the dynamic spatial expression of hox11/13b in each developmental phase. Several binding sites execute multiple, sometimes contradictory, regulatory functions, depending on the temporal and spatial regulatory context. In addition, we identified a nearby second CRM operating in inter-modular AND logic with the first CRM to control hox11/13b expression in hindgut endoderm. Our results suggest a mechanism for continuous gene expression in response to changing developmental network functions that depends on sequential combinatorial regulation of individual CRMs.

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Teaser

Gene expression is controlled by developmentally changing regulatory states. Cui et al. now find that the dynamic patterns of hox11/13b expression in response to distinct regulatory states during sea urchin endoderm development are controlled by sequentially operating transcription factor binding sites within an intronic cis-regulatory module.


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