TRANSCompel(R): a database on composite regulatory elements in eukaryotic genes

Kel-Margoulis, Olga V.; Kel, Alexander; Reuter, Ingmar; Deineko, I. V.; Wingender, Edgar

doi:10.1093/nar/30.1.332

Cited by 120 publications

(92 citation statements)

References 6 publications

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“…Physical Binding of Ets-1 to Pit-1 Is Not a Primary Determinant for Ras Responsiveness or Synergy-The assembly of transcription factors on composite elements is typically driven by vicinal DNA sites that bind these factors via protein-DNA interactions and stabilized via protein-protein interactions (37,41,42). We have shown previously by GST interaction assays and NMR analysis that the homeodomain of Pit-1 (amino acids 199 -291) interacts directly with the RIII TAD of chicken cEts-1 (amino acids 190 -257), albeit weakly (K d ϳ300 M) (12,13).…”

Section: Pit-1 Monomer Versus Dimer Dna Binding Sites Are Not a Primamentioning

confidence: 99%

Ras Signaling and Transcriptional Synergy at a Flexible Ets-1/Pit-1 Composite DNA Element Is Defined by the Assembly of Selective Activation Domains

Duval

Jean

Gutierrez‐Hartmann

2003

Journal of Biological Chemistry

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Pit-1 and Ets-1 binding to a composite element synergistically activates and targets Ras-mitogen-activated protein kinase signaling to the rat prolactin promoter. These transcriptional responses appear to depend on three molecular features: organization of the Ets-1/Pit-1 composite element, physical interaction of these two factors via the Pit-1 homeodomain (amino acids 199 -291) and the Ets-1 regulatory III domain (amino acids 190 -257), and assembly of their transcriptional activation domains (TADs). Here we show that the organization of the Ets-1/Pit-1 composite element tolerates significant flexibility with regard to Ras stimulation and synergy. Specifically, the putative monomeric Pit-1 binding site can be substituted with bona fide binding sites for either a Pit-1 monomer or dimer, and these sites tolerated a separation of 28 bp. Additionally, we show that the physical interaction of Ets-1 and Pit-1 is not required for Ras responsiveness or synergy because block mutations of the Pit-1 interaction surface in Ets-1, which reduced Ets-1/Pit-1 binding in vitro, did not significantly affect Ets-1 stimulation of Ras responsiveness or synergy. We also show differential use of distinct TAD subtypes and Pit-1 TAD subregions to mediate either synergy or Ras responsiveness. Specifically, TADs from Gal4, VP16, or Ets-2 regulatory III domain linked to Ets-1 DNA binding domain constructs restored synergy to these TAD/Ets-1 DNA binding domain fusions. Conversely, deletion of the defined Pit-1 TAD (amino acids 2-80) retained synergy, but not Ras responsiveness. Consequently, we further defined the Pit-1 amino-terminal TAD into region 1 (R1, amino acids 2-45) and region 2 (R2, amino acids 46 -80). R1 appears to regulate basal and synergistic responses, whereas the Ras response was mapped to R2. In summary, Ras responsiveness and Pit-1/Ets-1 synergy are mediated through the assembly of distinct TADs at a flexible composite element, indicating that different mechanisms underlie these two transcriptional responses and that the Pit-1 R2 subregion represents a novel, tissue-specific Ras-responsive TAD.

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Section: Pit-1 Monomer Versus Dimer Dna Binding Sites Are Not a Primamentioning

confidence: 99%

Ras Signaling and Transcriptional Synergy at a Flexible Ets-1/Pit-1 Composite DNA Element Is Defined by the Assembly of Selective Activation Domains

Duval

Jean

Gutierrez‐Hartmann

2003

Journal of Biological Chemistry

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“…The TRANSCompel database on composite regulatory elements in eukaryotic genes provides information on composite elements, containing two closely situated binding sites for distinct transcription factors, within a particular gene and experimental results confirming cooperative action between the transcription factors (Kel-Margoulis et al 2002b). Similarly, the Transcription Regulatory Regions Database (TRRD) contains information on genes, transcription-factor-binding sites, regulatory regions, locus control regions, and expression patterns (Kolchanov et al 2002).…”

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confidence: 99%

A Motif Co-Occurrence Approach for Genome-Wide Prediction of Transcription-Factor-Binding Sites inEscherichia coli

Bulyk¹,

McGuire²,

Masuda³

et al. 2004

Genome Res.

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Various computational approaches have been developed for predicting cis-regulatory DNA elements in prokaryotic genomes. We describe a novel method for predicting transcription-factor-binding sites in Escherichia coli. Our method takes advantage of the principle that transcription factors frequently coregulate gene expression, but without requiring prior knowledge of which groups of genes are coregulated. Using position weight matrices for 49 known transcription factors, we examined spacings between pairs of matrix hits. These pairs were assigned probabilities according to the overrepresentation of their separation distance.

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“…In addition to the more 'planar' CLASS table a hierarchical factor classification system is also used. TRANSCompel® originates from COMPEL, and functions to emphasize the key role of specific interactions between transcription factors binding to their target cis-regulatory elements; whilst providing specific features of gene regulation in a particular cellular content (Kel-Margoulis et al, 2002). Information about the structure of known trans factor and cis sequence interactions, and specific gene regulation achieved through these interactions, is extremely useful for promoter prediction.…”

Section: Bioinformatic Tools and Synthetic Promoter Developmentmentioning

confidence: 99%

The Use of Functional Genomics in Synthetic Promoter Design

Roberts¹

2011

Computational Biology and Applied Bioinformatics

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TRANSCompel(R): a database on composite regulatory elements in eukaryotic genes

Cited by 120 publications

References 6 publications

Ras Signaling and Transcriptional Synergy at a Flexible Ets-1/Pit-1 Composite DNA Element Is Defined by the Assembly of Selective Activation Domains

Ras Signaling and Transcriptional Synergy at a Flexible Ets-1/Pit-1 Composite DNA Element Is Defined by the Assembly of Selective Activation Domains

A Motif Co-Occurrence Approach for Genome-Wide Prediction of Transcription-Factor-Binding Sites inEscherichia coli

The Use of Functional Genomics in Synthetic Promoter Design

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