An ORFeome-based Analysis of Human Transcription Factor Genes and the Construction of a Microarray to Interrogate Their Expression

Messina, David N.; Glasscock, Jarret; Gish, Warren; Lovett, Michael

doi:10.1101/gr.2584104

Cited by 133 publications

(109 citation statements)

References 41 publications

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“…There are >20 identified families whose members have conserved DNA-binding domains and common binding properties (Messina et al 2004). The only mammalian transcription factor family with more than one member assayed by ChIP-chip is the six-member E2F family (Ren et al 2002;Weinmann et al 2002;Oberley et al 2003;Wells et al 2003).…”

Section: General Rules For Gene Familiesmentioning

confidence: 99%

“…Large gene families in mammalian genomes that encode transcription factors with highly related DNAbinding properties (e.g., ETS, GATA, HOX, or FOX proteins, and nuclear hormone receptors) (Messina et al 2004) present a further challenge. The dilemma is how transcription factors with overlapping DNA sequence preferences direct distinct transcriptional responses in vivo.…”

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confidence: 99%

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Genome-wide analyses reveal properties of redundant and specific promoter occupancy within theETSgene family

et al. 2007

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The conservation of in vitro DNA-binding properties within families of transcription factors presents a challenge for achieving in vivo specificity. To uncover the mechanisms regulating specificity within the ETS gene family, we have used chromatin immunoprecipitation coupled with genome-wide promoter microarrays to query the occupancy of three ETS proteins in a human T-cell line. Unexpectedly, redundant occupancy was frequently detected, while specific occupancy was less likely. Redundant binding correlated with housekeeping classes of genes, whereas specific binding examples represented more specialized genes. Bioinformatics approaches demonstrated that redundant binding correlated with consensus ETS-binding sequences near transcription start sites. In contrast, specific binding sites diverged dramatically from the consensus and were found further from transcription start sites. One route to specificity was found-a highly divergent binding site that facilitates ETS1 and RUNX1 cooperative DNA binding. The specific and redundant DNA-binding modes suggest two distinct roles for members of the ETS transcription factor family.[Keywords: ETS; transcription; gene families; cooperative binding; promoter specificity; ChIP-chip] Supplemental material is available at www.genesdev.org.

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Section: General Rules For Gene Familiesmentioning

confidence: 99%

mentioning

confidence: 99%

Genome-wide analyses reveal properties of redundant and specific promoter occupancy within theETSgene family

et al. 2007

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“…Nevertheless, given the lack of binding site data for most transcription factors in both model organisms and the human genome, even imperfect binding site data would be extremely valuable. For example, recent analysis suggests that there are ∼1960 transcription factors, corresponding to ∼8% of genes, in the human genome 11 , and the sequence specificities and functions of most of these proteins have not yet been determined. This B1H system provides another tool in our arsenal for identifying the DNA-binding specificities of transcription factors, and thus predicting their target genes and genomic DNA regulatory elements.…”

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confidence: 99%

Discovering DNA regulatory elements with bacteria

Bulyk

2005

Nat Biotechnol

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With the availability of nearly a decade's worth of genome-scale gene expression profiling and the more recent sequencing of multiple higher eukaryotic genomes, attention is now shifting towards determining the regulatory mechanisms underlying these expression patterns. However, a major challenge in understanding these transcriptional regulatory networks has been the lack of DNA-binding site data for most transcription factors. Without binding site data, it is difficult to identify the target genes directly regulated by a given transcription factor and to identify the cis regulatory elements through which this regulation occurs. In this issue, Wolfe and colleagues 1 present their adaptation of a bacterial one-hybrid (B1H) system 2 for determining the DNA-binding specificities of transcription factors. Two important advantages of Wolfe's version of a B1H approach over the previously developed B1H selection system 3 are the incorporation of a negative selectable marker for improved background reduction, and the use of randomized candidate DNA binding sites, both of which have been employed in yeast one-hybrid selection 4 . Using this updated B1H system, the authors identified the DNAbinding site motifs for eight metazoan transcription factors, including one Drosophila protein (Odd-skipped (Odd)) whose DNA-binding specificity was previously unknown. Using these newly discovered binding site data, they then predicted and experimentally validated two new target genes of Odd.DNA-binding proteins are important broadly in both lower organisms and more complex metazoans, in numerous cellular processes such as transcription regulation, DNA repair, and replication. The largest class of these proteins are regulatory transcription factors, which by binding in a sequence-specific fashion to DNA-binding sites in the genome, modulate the expression of their target genes as required for normal progression through the cell cycle and in response to environmental stimuli, and in a cell type and developmental stage specific manner in higher organisms.Despite the crucial regulatory roles of transcription factors, the DNA-binding specificities of relatively few of them have been characterized in depth. In order to understand how they regulate their target genes, one must be able to identify the DNA-binding sites to which they bind in a given genome. Currently, experimental data on transcription factors' DNA-binding specificities are required to predict such cis regulatory elements. However, some methods for high-throughput binding site determination, such as microarray-based readout of chromatin immunoprecipitation ('ChIP-chip') 5-7 , require specific antibodies, while other methods, such as in vitro selection 8 and protein binding microarrays 9 , require purified protein. In contrast, the B1H system not only employs in vivo selection, but also offers a low-tech alternative to microarray-based technologies.

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“…Genes in each category were identified by their Gene Ontology (GO) classification (15). In addition, transcription factors reported in Messina et al (16) were taken directly from that paper. The GO classification of human genes was used and the mouse orthologue determined by using the Ensembl database.…”

Section: Methodsmentioning

confidence: 99%

“…We assessed the representation of classes of genes likely to be of particular interest and for which there were Ensembl-assigned human-mouse orthologues (16,27), including kinases, phosphatases, G proteincoupled receptors (GPCRs) and transcription factors (see Table 4, which is published as supporting information on the PNAS web site). Most of the genes within each of these classes were found in our data, with the exception of GPCR genes.…”

Section: Representation Of Gene Families Of Interestmentioning

confidence: 99%

A mouse atlas of gene expression: Large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells

Siddiqui

Khattra

Delaney

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

113

120

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We analyzed 8.55 million LongSAGE tags generated from 72 libraries. Each LongSAGE library was prepared from a different mouse tissue. Analysis of the data revealed extensive overlap with existing gene data sets and evidence for the existence of Ϸ24,000 previously undescribed genomic loci. The visual cortex, pancreas, mammary gland, preimplantation embryo, and placenta contain the largest number of differentially expressed transcripts, 25% of which are previously undescribed loci.alternative transcripts ͉ development ͉ serial analysis of gene expression

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An ORFeome-based Analysis of Human Transcription Factor Genes and the Construction of a Microarray to Interrogate Their Expression

Cited by 133 publications

References 41 publications

Genome-wide analyses reveal properties of redundant and specific promoter occupancy within theETSgene family

Genome-wide analyses reveal properties of redundant and specific promoter occupancy within theETSgene family

Discovering DNA regulatory elements with bacteria

A mouse atlas of gene expression: Large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells

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