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Contents

[edit] Gene Index

The TFCat Gene Index provides browsing access to all genes with annotations in the database. The list may be re-sorted by clicking on the icon at the top of desired sorting column.

[edit] Judgements Index

The scientific literature for each reviewed candidate transcription factor was assessed by one or more qualified scientists. The reviewers applied their best judgment, based on the literature they read, to assign annotations consistent with the described experiments. In each case, the reviewer assessed a measure of confidence based on the nature of the studies performed, the control experiments performed and any conflicting results between papers. In most cases it was not feasible to review the entirety of the scientific literature for a candidate transcription factor. If you believe the confidence misrepresents the evidence, we hope you will help the community of TFCat users by providing your feedback.

[edit] Taxonomy Index

Positively judged genes were assigned to one or more functional taxa based on the evidence provided in the literature reviewed.

[edit] DBD Classification

The TFCat DNA Binding Domain classification is based on the structural classification system developed by Luscombe and Thornton (see link). The system features 7 broad protein groups and within each group are protein families reflecting subdivisions of the group. The Luscombe system allows for families to be defined based on functional and structural properties. In order to incorporate additional DNA binding proteins not supported in the original Luscombe report, we have added new structural-based families to the existing protein groups. Please read the TFCat paper for details.

[edit] Homolog Clusters

As manual curation of all possible TF candidates is challenging given the curation effort and literature evidence constraints, we endeavored to supplement our collection of TF families with predicted TFs homologs. To enable access to a list (family) of homologous TFs, we have identified and clustered candidate homologs. The specific implementation of the search procedure is described in the TFCat paper. We recognize that the prediction of homology relationships is often the basis for significant debate in some communities. The TFCat collection is freely available for those interested parties to re-assess the homology relationships and we welcome feedback about alternative groupings of genes.

[edit] Searching

To expand the data searching capabilities, we have implemented the Semantic MediaWiki tool along with the MediaWiki software. Therefore, the TFCatWiki system supports both general text searching and field tag-specific searching. For information on the Semantic Mediawiki tool, please see this link.

[edit] Quick Search

The quickest way to search for a gene page is to enter a descriptor for that gene, such as: gene id or gene symbol or a partial descriptor.

[edit] Search Forms

Search forms enable more complex custom queries. The following attributes are available for searching:

  • Gene description
  • Gene id
  • Gene judgment
  • Gene symbol
  • Gene taxonomy
  • Homolog cluster
  • Protein group (DBD Classification group level)
  • Protein family (DBD Classification family level)


Each TFCatWiki gene page lists its defined attributes and their values.


Inline Query Form
Inline queries support gene queries by (multiple) attributes (see list above) and selected values. For instruction on how to setup an inline query, see this link


Attribute Search Form
The Attribute Search Form enables gene queries by attribute name (listed above) and value.


[edit] Annotation Reviewer Guidelines

The following reviewer guidelines were provided as a reference during our annotation process.

[edit] I) Guide to Establishing Judgement and Functional (Taxonomy) Classifications

Transcription Factor: A protein that plays a nuclear role in initiating the transcription of genes. Includes DNA binding (specific or non-specific) proteins and proteins that physically interact with DNA binding proteins in DNA-containing complexes. Deliberately does not include proteins which are restricted to the cytoplasm, nor proteins which can perform their function without coming into physical contact with DNA or proteins bound to DNA.

General Guide To Determining Transcription Regulatory Activity
Transcription factors are able to increase or decrease the rate of transcription from a native or synthetic gene promoter. Studies showing that a protein represses gene transcription should be interpreted with care. Repression demonstrated by cotransfection assays may result from competition for a DNA binding site on the reporter construct or by squelching (overexpression of the transfected protein sequesters a component essential for gene activation, resulting in decreased transcriptional activity). While the first mechanism suggests that the protein either interferes with DNA binding by other transcription factors or that it might contain a DNA binding domain that competes for regulatory sites in the promoter, neither mechanism demonstrates that the protein is an active transcriptional repressor. In addition, a protein's ability to repress transcription depends heavily on the promoter contexts: most transcriptional repressors will activate some other promoter. As a result, it's important to identify the promoter or synthetic construct that is used to demonstrate transcriptional repression.

Evidence for a protein's transcriptional activation/repression property is usually provided by transient transfection assays using either the intact protein or chimeric proteins containing deletion mutants fused to a heterologous DNA binding domain. Transactivation/transrepression may also be demonstrated using in vitro transcription assays (including studies of preinitiation complex formation or transcription elongation) or stable transfections. Microarray studies, particularly those showing an alteration in expression profiles following stable expression or knockout/knockdown of the TF are usually not good evidence. Similarly, Western blots and Northern blots and studies demonstrating protein-protein interactions with general transcription factors or coactivators may provide suggestive evidence; however, direct functional studies are preferable.

Judgement Guidelines

  • TF Gene
    The protein conclusively belongs in one or more of the TF functional categories listed below.
  • TF Gene Candidate

    There is evidence that the protein is involved in transcription regulation but its regulatory role as a transcription factor was not clearly demonstrated. This judgment may accompany functional TF category assignments. This judgement category is not to be used for homology inference.

  • Probably Not a TF: No Evidence that it is a TF

    After review of the available data, there is insufficient evidence or currently no indication that the protein belongs in any of the TF functional categories. This is essentially a repudiation of the original nomination of the protein.

  • Not a TF: Evidence that it is not a TF

    Despite the original reason for nomination, there is clear evidence that makes it highly unlikely that the protein has a transcription factor role.

  • TF Evidence Conflict

    There exists evidence both for and against the function of the protein, and the reviewer is unable to render a final decision due to the conflict (this is an undesirable category, and should be seldom used).


Functional Classification (Taxonomy) Guidelines

  • Transcription Regulatory Activity: Heterochromatin Interaction/ Binding
    The protein is a transcription factor and is also shown to co-localize with heterochromatin.
  • DNA-Binding: Sequence specific

    The protein binds to specific DNA sequences. This would require evidence of binding such as a transactivation assay performed using binding site mutants or as part of a one-hybrid experiment, gel shift (EMSA), DNase I or Exonuclease III footprinting, methylation protection/interference assays, UV crosslinking, Southwestern blotting, or selection/amplification experiments. In all cases, there would need to be appropriate controls showing that there are DNA sequences to which the protein will NOT bind.

  • DNA-Binding: Sequence non-specific

    The protein binds to DNA in general or to structural motifs such as DNA hairpins. (All sequence specific DNA binding proteins have a weak affinity for DNA in general, so this category more accurately refers to DNA binding proteins which exhibit no marked preference for subsets of sequences. Experiments for non-specific DNA binding might include transactivation assays, gel shift, UV crosslinking, chromatin IP, heparin binding, and DNA affinity chromatography techniques.

  • TF Binding: TF Co-factor binding

    The protein interacts (directly or indirectly within a complex) with another protein which is bound to DNA. As sequence specific DNA binding proteins often physically interact with one-another, I recommend that we exclude sequence-specific DNA binding proteins from this category. Evidence might be from 2-hybrid studies, co-immunoprecipitation (or other pull-down methods), or Southwestern blotting.

  • Basal TF

    A protein which contributes to the initiation of transcription, but does not primarily act in modulating the rate of transcription from one state to another. This category would include all members of the RNA polymerase complex. Could have DNA binding activity or not. Co-purifies with basal transcription machinery such as polymerase. Basal TFs are frequently required for in vitro transcription reaction.

[edit] II) Guide to PubMed and Reviewer Comments

PubMed and Reviewer Comments are a critical part of the Transcription Factor Resource. They provide concise descriptions of the functional properties of proteins listed in the database. Reviewer comments summarize evidence contained in published literature that supports the key properties of transcription factors, including their ability to bind DNA, their transactivation or transrepression potential and their ability to interact with other proteins or molecules that regulate gene transcription.

PubMed Comments are designed to be used internally in the Transcription factor resource project (but will form part of the public database - similar to the "Discussion" section of a Wiki). They contain one or more sentences describing the evidence contained in a single paper that support a particular functional property for a specific gene transcript. They should identify the technique used, whether the experiment identified the property of interest or demonstrated its absence and provide some evidence of the quality of the study. The study quality should be assessed in terms of the appropriateness of the technique as well as in terms of the technical quality of the figures (please be careful to be polite). In addition, the PubMed comments can be used to keep track of conflicting lines of evidence as well as to record results that were unclear or that need further review. In general, try to keep the Pubmed comments simple. Write straightforward sentences that discuss a single property of transcript and that clearly indicate whether this property was demonstrated convincingly or not. In addition, where possible, try to review at least two relevant papers for each gene.

Here are examples of some PubMed comments:

  • GeneID: 11614 (Nuclear receptor subfamily 0, group B, member 1)
    Referring to PMID: 9661652 Function: Transactivation (Strong)
    Comment: Transient transfection assays performed with a chimeric gal4DBD-DAX1 fusion protein identify a transcriptional repression domain in the DAX-1 C-terminus.

  • GeneID: 11614 (Nuclear receptor subfamily 0, group B, member 1)

    Referring to PMID: 11053406
    Function: Co-activation (Strong)
    Comment: NR0B1 binds to ER-alpha and ER-beta by co-immunoprecipitation assays. Transfection assays show Nr0b1 is a corepressor of ER-alpha and ER-beta.

  • GeneID: 11614 (Nuclear receptor subfamily 0, group B, member 1)

    Referring to PMID: 9384387
    Function: DNA-Binding: non-sequence-specific (Strong)
    Comment: DAX-1 efficiently recognizes DNA hairpin structures in vitro. It binds equally efficiently to stems composed of 10 to 24 nucleotides. The binding shows no strong sequence specificity.

Reviewer Comments will be published as part of the Transcription Factor Resource. They should contain a concise summary of the functional properties of the gene transcript including a description of functional differences that exist between isoforms. Reviewer comments should indicate clearly whether or not the transcript is a transcription factor. They don't need to describe the transcript's general biologic properties (such as its role in development or normal cell physiology); however, they should provide a clear evidence-based justification of your decision.

When writing your comments, please keep the following advice in mind:

  1. Full sentences are easier to understand than sentence fragments.
  2. Use the present tense for verbs.
  3. Avoid complex sentence structures: simple sentences (subject verb

    object) are clearer.

  4. Write a single sentence for each line of experimental evidence.
  5. Indicate clearly the technique and biologic substrate that was

    used to obtain the evidence.

  6. Identify genes using their EntrezGene identifiers rather than by

    nicknames or synonyms.

  7. Write descriptions to convey complete thoughts independently of

    other information presented for the gene.

Here are some examples of Reviewer Comments:

  • GeneID: 11634 (Autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy))
    Reviewer Judgement: TF Gene
    Reviewer Comment: Aire is a transcripton factor. It shows in vitro DNA binding through gel shift assays and binding to a G2N7G2 oligonucleotide library. It transactivates a reporter gene when fused to a heterologous DNA binding domain and interacts with CBP in a GST-pulldown assay. Transient transfection studies show that Aire activates transcription of the interferon-beta gene.

  • GeneID: 73916 (Estrogen-related receptor beta like 1)

    Reviewer Judgement: Not a TF - Evidence that it is not a TF
    Reviewer Comment: The Esrrbl1 transcript displays sequence homology to members of the nuclear receptor superfamily. The proteins are not homologous and the transcript does not encode a nuclear receptor DNA binding domain.

  • GeneID: 11614 (Nuclear receptor subfamily 0, group B, member 1)

    Reviewer Judgement: TF Gene
    Reviewer Comment: Dax-1 efficiently recognizes DNA hairpin structures in vitro and binds efficiently to stems composed of 10 to 24 nucleotides, but not to response elements with shorter stems. Dax-1 DNA binding shows no strong sequence specificity. Dax-1 represses StAR expression and consequently suppresses steroidogenesis by binding to a hairpin in the StAR promoter (transfection assay). Fusion of the DAX-1 carboxy terminus to the GAL4 DNA-binding domain (DBD) results in a protein that efficiently represses a globin promoter containing GAL4-binding site.

Taken together, the PubMed and Reviewer Comments should provide a wealth of core information to the TF community that can be extended as science progresses. Try to keep your colleagues in mind as you write them - providing useful and interesting information for a large number of Transcription Factors will help to increase the scientific impact of the Transcription Factor Resource.

[edit] Contacting Us

If you wish to provide feedback regarding the annotation data, please use our feedback tracking system available [here]. See the Feedback Tracking Help for more information and access to help.

Otherwise, you may reach us at: tfcat@cmmt.ubc.ca

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