Dear Reyaneh,

Perhaps the first step is to map the position o the mutation onto the protein sequence of the wild-type protein, and to look at the literature to see if the DNA-binding domains have been mapped. You could also look at UniProt (www.uniprot.org) to see if your transcription factor is listed, as this will also indicate domains and active stiles etc. (you could look of the domains yourself using HMMERScan (www.ebi.ac.uk/Tools/hmmer/search/hmmscan) too).

If your mutation is in a DNA-binding domain then it is possible that your mutant transcription factor won't bind properly. You could look into this further, as it is possible that there is a co-crystal structure of the transcription factor with the DNA site. If you can access the PDB file, you can look to see where the position of the residue that has changed is in relation to the DNA molecule, and whether or not it forms bonds with particular bases.

Andrew

Transcription factors (TFs) bind to regulatory DNA to control gene expression. Mutations to either TFs or DNA can alter binding affinities.

ChIP-seq is the most commonly used experimental method to determine specific regions of DNA where TFs bind

Mutations in TFs and TF-binding sites underlie many human diseases.

TFs are either tumor suppressors or oncogenes.

Mutations or aberrant regulation of TFs are associated with cancer.

Mutations in TFs can cause:

Developmental abnormalities

Cancer

Neurodegeneration

Ocular defects at birth

Inherited photoreceptor diseases

Other tools that can be used to infer transcription factor activity include Gene expression and Information on transcription factor (TF) binding.

rSNP_Guide is being investigated as a tool for TF site annotation. It investigates the influence of mutations in regulatory gene regions onto DNA interaction.

Dear Andrew J Spiers and Susanta Roy,

Thank you very much for your answers.