title: Sequential Response to Multiple Developmental Network Circuits Encoded in an Intronic cis-Regulatory Module of Sea Urchin hox11/13b.
abstract: 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.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: miao.cui@ucsf.edu.
authors.forename: Miao
authors.initials: M
authors.lastname: Cui
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Vielmas
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Davidson
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: ipeter@caltech.edu.
authors.forename: Isabelle S
authors.initials: IS
authors.lastname: Peter
mesh_terms: D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D007438:Introns / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012617:Sea Urchins / Q000235:genetics / Q000254:growth & development*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins
keywords: Boolean modeling; developmental gene expression; gene regulatory networks; transcriptional control