Immunity Regulatory DNAs Share Common Organizational Features in Drosophila

Senger, Kate; Armstrong, Grant W; Rowell, William J; Kwan, Jennifer M.; Markstein, Michele; Levine, Michael

doi:10.1016/s1097-2765(03)00500-8

Cited by 140 publications

(158 citation statements)

References 41 publications

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“…c) The ZnFp53 motif is consistent with the previously described consensus sequence ((g/a)GACACGT) determined by SELEX for a nearly identical clone 12 . d) The Dorsal motif is consistent with the previously described consensus sequence (GGG(a/t)(a/t)(t/a)(t/c/a)C(c/t)) determined by SELEX 16 . e) The LAG-1 motif is consistent with the previously described consensus sequence (A(c/g)CGTGGGAA(a/c)) for the mouse homolog of LAG-1 (RBP-Jκ) determined by SELEX 18 .…”

Section: Supplementary Materialssupporting

confidence: 87%

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A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors

2005

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The DNA-binding specificities of transcription factors can be used to computationally predict cisregulatory modules (CRMs) that regulate gene expression 1 . However, the absence of specificity data for the majority of transcription factors limits the wide-spread implementation of this approach. We have developed a bacterial one-hybrid system that provides a simple and rapid method to determine the DNA-binding specificity of a transcription factor. Using this technology, we successfully determined the DNA-binding specificity of seven previously characterized transcription factors and one novel transcription factor, the Drosophila factor Odd-skipped. Regulatory targets of Odd-skipped were successfully predicted using this information, demonstrating that the data produced by the bacterial one-hybrid system is relevant to in vivo function.Several methods exist for determining the DNA-binding specificity of a transcription factor. SELEX is the most commonly employed method to define DNA-binding specificity 2 . More recently, microarrays of short oligonucleotides 3 or intergenic sequences 4 have been used to characterize transcription factors. Genome-wide chromatin immunoprecipitation (ChIPchip) 5 and DNA immunoprecipitation with microarray detection (DIP-chip) 6 have also been used in conjunction with computational analysis to identify statistically overrepresented sequence motifs to extract DNA-binding specificity from the genomic segments that are bound by a transcription factor. These methods, while powerful, have drawbacks: the in vitro technologies require the purification of the transcription factor in its active form; SELEX requires multiple rounds of selection to complete; and microarray-based techniques require the facilities and expertise to analyze the arrays and resulting data.We have developed a bacterial one-hybrid (B1H) system that provides a simple method for defining the DNA-binding specificity of a transcription factor. The selection procedure is rapid, because only a single round of selection is required to generate a set transcription factor binding sites, and it is readily accessible, because only basic molecular biology expertise is required to employ the technology. Conceptually, this system is similar to yeast one-hybrid systems that can determine the DNA-binding specificity of a transcription factor 7 and detect protein-DNA interactions 8 . However, a bacterial selection system provides advantages over the

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Section: Supplementary Materialssupporting

confidence: 87%

“…The binding site motif constructed from sequences isolated using the Dorsal bait (Fig. 2d) is similar to the specificity previously determined by SELEX for this domain 16 . LAG-1 from C. elegans contains a CSL-type DNA-binding domain 17 .…”

supporting

confidence: 72%

A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors

2005

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“…In Drosophila, the regulation of a large number of innate immune response genes can indeed be accounted for by the combinatorial regulation of NF-kB and the GATA factor serpent (Senger et al, 2004). By measuring DNA-binding affinities of these factors for diverse binding sites, it may be possible to construct a predictive model for the regulatory code.…”

Section: Transcriptional Specificity As Determined By Nf-jb Dynamicsmentioning

confidence: 99%

Transcriptional regulation via the NF-κB signaling module

2006

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Stimulus-induced nuclear factor-jB (NF-jB) activity, the central mediator of inflammatory responses and immune function, comprises a family of dimeric transcription factors that regulate diverse gene expression programs consisting of hundreds of genes. A family of inhibitor of jB (IjB) proteins controls NF-jB DNA-binding activity and nuclear localization. IjB protein metabolism is intricately regulated through stimulus-induced degradation and feedback re-synthesis, which allows for dynamic control of NF-jB activity. This network of interactions has been termed the NF-jB signaling module. Here, we summarize the current understanding of the molecular structures and biochemical mechanisms that determine NF-jB dimer formation and the signal-processing characteristics of the signaling module. We identify NF-jB-jB site interaction specificities and dynamic control of NF-jB activity as mechanisms that generate specificity in transcriptional regulation. We discuss examples of gene regulation that illustrate how these mechanisms may interface with other transcription regulators and promoter-associated events, and how these mechanisms suggest regulatory principles for NF-jB-mediated gene activation.

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“…With few exceptions (Erives and Levine, 2004;Markstein et al, 2004;Senger et al, 2004), the architecture of binding sites in an enhancer, and the nature of interactions among transcription factors that regulate its activity, are not understood well enough to predict the consequences of specific cis-regulatory changes from sequence alone. Empirical tests are required to determine cis-regulatory function and to assess the impact of sequence divergence on gene expression.…”

Section: Molecular Evolution Of Cis-regulatory Sequencesmentioning

confidence: 99%

Evolution of cis-regulatory sequence and function in Diptera

Wittkopp

2006

Heredity

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Cis-regulatory sequences direct patterns of gene expression essential for development and physiology. Evolutionary changes in these sequences contribute to phenotypic divergence. Despite their importance, cis-regulatory regions remain one of the most enigmatic features of the genome. Patterns of sequence evolution can be used to identify cisregulatory elements, but the power of this approach depends upon the relationship between sequence and function. Comparative studies of gene regulation among Diptera reveal that divergent sequences can underlie conserved expression, and that expression differences can evolve despite largely similar sequences. This complex structure-function relationship is the primary impediment for computational identification and interpretation of cis-regulatory sequences. Biochemical characterization and in vivo assays of cis-regulatory sequences on a genomic-scale will relieve this barrier.

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Immunity Regulatory DNAs Share Common Organizational Features in Drosophila

Cited by 140 publications

References 41 publications

A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors

A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors

Transcriptional regulation via the NF-κB signaling module

Evolution of cis-regulatory sequence and function in Diptera

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