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==== Definition  ====

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. 

==== [[Image:Image6.jpg]]<br><br>Evidence Matrix / 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). 

==== Homology-based Evidence ====

==== <br>'''''Classification''''' ====

Transcription Regulatory Activity – Heterochromatin Interaction Binding The protein is a transcription factor and is also shown to co-localize with heterochromatin. 

Transcription Regulatory Activity – Activation or Repression 

The protein is able to increase or decrease the rate of transcription from a native or synthetic gene promoter. Evidence 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. Transctivation/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. 

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-hydrid 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. 

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