De novo discovery of a tissue-specific gene regulatory module in a chordate

Johnson, D. S.; Zhou, Qing; Yagi, Keisuke; Satoh, Nori; Wong, Wing Hung; Sidow, Arend

doi:10.1101/gr.4062605

Cited by 32 publications

(25 citation statements)

References 27 publications

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“…Arend Sidow and David S. Johnson (Stanford University) reported the identification of shared sequence features among a set of 20 different muscle-specific enhancers (Johnson et al 2005). Similarly, Take Kusakabe (University of Hyogo) presented evidence that distinct combinations of regulatory elements could be identified in tissue-specific enhancers mediating restricted expression in muscles, neurons, or photoreceptor cells.…”

Section: Bioinformatics Of Gene Regulationmentioning

confidence: 99%

Surfing with the tunicates into the post-genome era

Satoh

Levine

2005

Genes Dev.

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This year is the centenary of Edward G. Conklin's signal findings in embryology: the elucidation of complete cell lineages and the discovery of localized maternal determinants. Conklin used ascidian embryos to elucidate universal principles in embryology. A century later, ascidians, or sea squirts, have not only entered the postgenome era, but in many ways are leading the way to the promise of a "systems-level" understanding of complex processes such as notochord formation, neurogenesis, and even behavior.

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Section: Bioinformatics Of Gene Regulationmentioning

confidence: 99%

Surfing with the tunicates into the post-genome era

Satoh

Levine

2005

Genes Dev.

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“…Donaldson et al (2005) exploited detailed knowledge of critical binding site motifs and their spacing, along with human-rodent conservation and positive RP, to predict and validate novel enhancers for genes involved in mammalian hematopoiesis. Johnson et al (2005) used a combination of clusters of predicted motifs and evolutionary conservation successfully to identify muscle CRMs in a genome-wide scan of Ciona. Thus, the approach of combining RP scores with another feature of CRMs, such as conserved motifs or clusters of motifs, should be broadly applicable to studies of gene regulation in complex genomes.…”

Section: Discussionmentioning

confidence: 99%

Experimental validation of predicted mammalian erythroid cis-regulatory modules

et al. 2006

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Multiple alignments of genome sequences are helpful guides to functional analysis, but predicting cis-regulatory modules (CRMs) accurately from such alignments remains an elusive goal. We predict CRMs for mammalian genes expressed in red blood cells by combining two properties gleaned from aligned, noncoding genome sequences: a positive regulatory potential (RP) score, which detects similarity to patterns in alignments distinctive for regulatory regions, and conservation of a binding site motif for the essential erythroid transcription factor GATA-1. Within eight target loci, we tested 75 noncoding segments by reporter gene assays in transiently transfected human K562 cells and/or after site-directed integration into murine erythroleukemia cells. Segments with a high RP score and a conserved exact match to the binding site consensus are validated at a good rate (50%–100%, with rates increasing at higher RP), whereas segments with lower RP scores or nonconsensus binding motifs tend to be inactive. Active DNA segments were shown to be occupied by GATA-1 protein by chromatin immunoprecipitation, whereas sites predicted to be inactive were not occupied. We verify four previously known erythroid CRMs and identify 28 novel ones. Thus, high RP in combination with another feature of a CRM, such as a conserved transcription factor binding site, is a good predictor of functional CRMs. Genome-wide predictions based on RP and a large set of well-defined transcription factor binding sites are available through servers at http://www.bx.psu.edu/.

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“…The TFs that bind to cis-regulatory motifs are thought to interact cooperatively to drive promoter function (Johnson et al 2005). Therefore, a thorough characterization of these modules is a key step for understanding gene regulatory networks.…”

Section: Cis-regulatory Module Discoverymentioning

confidence: 99%

“…Promoters contain short sequence features, or motifs, to which transcription factors (TFs) bind and regulate transcription (Myers et al 1986;Johnson et al 2005;Cooper et al 2006;Brown et al 2007; The ENCODE Project Consortium 2007; Johnson et al 2007;Lin et al 2007). Large-scale efforts to identify and characterize human promoters are typically transcript-based, including aligning full-length cDNA sequences to the genome (Imanishi et al 2004), mapping 59 ends by CAGE tags (Shiraki et al 2003), and performing gene expression microarray analyses (Su et al 2002(Su et al , 2004.…”

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confidence: 99%

Sequence features that drive human promoter function and tissue specificity

Landolin¹,

Johnson²,

Trinklein³

et al. 2010

Genome Res.

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Promoters are important regulatory elements that contain the necessary sequence features for cells to initiate transcription. To functionally characterize a large set of human promoters, we measured the transcriptional activities of 4575 putative promoters across eight cell lines using transient transfection reporter assays. In parallel, we measured gene expression in the same cell lines and observed a significant correlation between promoter activity and endogenous gene expression (r = 0.43). As transient transfection assays directly measure the promoting effect of a defined fragment of DNA sequence, decoupled from epigenetic, chromatin, or long-range regulatory effects, we sought to predict whether a promoter was active using sequence features alone. CG dinucleotide content was highly predictive of ubiquitous promoter activity, necessitating the separation of promoters into two groups: high CG promoters, mostly ubiquitously active, and low CG promoters, mostly cell line-specific. Computational models trained on the binding potential of transcriptional factor (TF) binding motifs could predict promoter activities in both high and low CG groups: average area under the receiver operating characteristic curve (AUC) of the models was 91% and exceeded the AUC of CG content by an average of 23%. Known relationships, for example, between HNF4A and hepatocytes, were recapitulated in the corresponding cell lines, in this case the liver-derived cell line HepG2. Half of the associations between tissue-specific TFs and cell line-specific promoters were new. Our study underscores the importance of collecting functional information from complementary assays and conditions to understand biology in a systematic framework.

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De novo discovery of a tissue-specific gene regulatory module in a chordate

Cited by 32 publications

References 27 publications

Surfing with the tunicates into the post-genome era

Surfing with the tunicates into the post-genome era

Experimental validation of predicted mammalian erythroid cis-regulatory modules

Sequence features that drive human promoter function and tissue specificity

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