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Published April 11, 2017 | Supplemental Material + Published
Journal Article Open

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


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.

Additional Information

© 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 4 November 2016. Revised 27 January 2017. Accepted 13 March 2017. Available online 11 April 2017. In memory of E.H.D. (1937–2015). We thank Peng He, Say-Tar Goh, and Brian Williams for discussions and experimental assistance with 4C-seq; Alexias Safi, Gregory Crawford, and Greg Wray for their contributions to the ATAC-seq experiment; and Andrew Cameron and Parul Kudtarkar for assistance on ATAC-seq data analysis and the maintenance of the sea urchin genome browser. This work was funded by NIH Grant HD 037105.2211124717303856). Author Contributions: Conceptualization, M.C. and I.S.P.; Investigation, M.C. and E.V.; Writing – Original Draft, M.C. and I.S.P.; Writing – Review & Editing, M.C. and I.S.P., Funding Acquisition, E.H.D. and I.S.P.

Attached Files

Published - 1-s2.0-S2211124717303856-main.pdf

Supplemental Material - mmc1.pdf

Supplemental Material - mmc2.pdf


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