title: Single embryo-resolution quantitative analysis of reporters permits multiplex spatial cis-regulatory analysis.
abstract: Cis-regulatory modules (CRMs) control spatiotemporal gene expression patterns in embryos. While measurement of quantitative CRM activities has become efficient, measurement of spatial CRM activities still relies on slow, one-by-one methods. To overcome this bottleneck, we have developed a high-throughput method that can simultaneously measure quantitative and spatial CRM activities. The new method builds profiles of quantitative CRM activities measured at single-embryo resolution in many mosaic embryos and uses these profiles as a 'fingerprint' of spatial patterns. We show in sea urchin embryos that the new method, Multiplex and Mosaic Observation of Spatial Information encoded in Cis-regulatory modules (MMOSAIC), can efficiently predict spatial activities of new CRMs and can detect spatial responses of CRMs to gene perturbations. We anticipate that MMOSAIC will facilitate systems-wide functional analyses of CRMs in embryos.
authors.affiliation: Center for Computational & Integrative Biology, Rutgers, The State University of New Jersey, Camden, NJ 08102, USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Guay
authors.affiliation: Center for Computational & Integrative Biology, Rutgers, The State University of New Jersey, Camden, NJ 08102, USA.
authors.forename: Sean T
authors.initials: ST
authors.lastname: McQuade
authors.affiliation: Center for Computational & Integrative Biology, Rutgers, The State University of New Jersey, Camden, NJ 08102, USA; Department of Biology, Rutgers, The State University of New Jersey, Camden, NJ 08102, USA. Electronic address: jn322@camden.rutgers.edu.
authors.forename: Jongmin
authors.initials: J
authors.lastname: Nam
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics; D058893:DNA Barcoding, Taxonomic / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D012313:RNA / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D012617:Sea Urchins / Q000196:embryology*; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D012313:RNA; D004247:DNA
keywords: Cis-regulatory; Embryo; Gene regulatory network; High-throughput; Mosaic; Reporter assay; Sea urchin; Spatial