ArticleProceedings of the National Academy of Sciences of the United States of America2010
Functional cis-regulatory genomics for systems biology.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Nrf1 coordinates proteasome activity and autophagy to maintain cardiac proteostasis.Communications biology · 2026Article
- Deep conservation of cis-regulatory elements and chromatin organization in echinoderms uncover ancestral regulatory features of animal genomes.Nature ecology & evolution · 2026Article
- Senolytics and cell senescence: historical and evolutionary perspectives.Evolution, medicine, and public health · 2024Article
- Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development.Developmental cell · 2023Article
- Quantitative-enhancer-FACS-seq (QeFS) reveals epistatic interactions among motifs within transcriptional enhancers in developing Drosophila tissue.Genome biology · 2021Article
- Article
- miRNA-independent function of long noncoding pri-miRNA loci.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Developmental effector gene regulation: Multiplexed strategies for functional analysis.Developmental biology · 2019Article
- Bacterial artificial chromosomes as recombinant reporter constructs to investigate gene expression and regulation in echinoderms.Briefings in functional genomics · 2018Review
- Simple Expression Domains Are Regulated by Discrete CRMs DuringG3 (Bethesda, Md.) · 2017Article
- Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The analysis of novel distal Cebpa enhancers and silencers using a transcriptional model reveals the complex regulatory logic of hematopoietic lineage specification.Developmental biology · 2016Article
- Eric Davidson: Steps to a gene regulatory network for development.Developmental biology · 2016Article
- Understanding how cis-regulatory function is encoded in DNA sequence using massively parallel reporter assays and designed sequences.Genomics · 2015Review
- FIREWACh: high-throughput functional detection of transcriptional regulatory modules in mammalian cells.Nature methods · 2014Article
- Function-based identification of mammalian enhancers using site-specific integration.Nature methods · 2014Article
- High throughput microinjections of sea urchin zygotes.Journal of visualized experiments : JoVE · 2014Article
- Article
- Developmental cis-regulatory analysis of the cyclin D gene in the sea urchin Strongylocentrotus purpuratus.Biochemical and biophysical research communications · 2013Article
- New regulatory circuit controlling spatial and temporal gene expression in the sea urchin embryo oral ectoderm GRN.Developmental biology · 2013Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Gene expression is controlled by interactions between trans-regulatory factors and cis-regulatory DNA sequences, and these interactions constitute the essential functional linkages of gene regulatory networks (GRNs). Validation of GRN models requires experimental cis-regulatory tests of predicted linkages to authenticate their identities and proposed functions. However, cis-regulatory analysis is, at present, at a severe bottleneck in genomic system biology because of the demanding experimental methodologies currently in use for discovering cis-regulatory modules (CRMs), in the genome, and for measuring their activities. Here we demonstrate a high-throughput approach to both discovery and quantitative characterization of CRMs. The unique aspect is use of DNA sequence tags to "barcode" CRM expression constructs, which can then be mixed, injected together into sea urchin eggs, and subsequently deconvolved. This method has increased the rate of cis-regulatory analysis by >100-fold compared with conventional one-by-one reporter assays. The utility of the DNA-tag reporters was demonstrated by the rapid discovery of 81 active CRMs from 37 previously unexplored sea urchin genes. We then obtained simultaneous high-resolution temporal characterization of the regulatory activities of more than 80 CRMs. On average 2-3 CRMs were discovered per gene. Comparison of endogenous gene expression profiles with those of the CRMs recovered from each gene showed that, for most cases, at least one CRM is active in each phase of endogenous expression, suggesting that CRM recovery was comprehensive. This approach will qualitatively alter the practice of GRN construction as well as validation, and will impact many additional areas of regulatory system biology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.