What Is The Average Length Of Transcription Factor Binding Site(S) In Human ?

Question

[Khader Shameer]

Background section of this manuscript gives hints about average length or specificity of cis-regulatory elements in E. coli and fly. I would like to know similar numbers for mouse and human.

For example, it is not clear what controls the length or specificity of cis-regulatory elements. These two properties appear to differ greatly between bacteria and eukaryotes; in Escherichia coli the average length of a consensus motif is 24.5 base pairs (bp) [1], whereas the average motif length in the fruit fly Drosophila is only 12.5 bp [2].

Given that both ENCODE and modENCODE data is around for a long time, am sure someone might have done an analysis or mentioned it in article. Let me know if you know about a manuscript / review article.

Answer 1

[Casey Bergman]

Published empirical data on this point is surprisingly rare, and people generally report numbers without providing a hard citation. The general argument is that steric constraints imposed by the ~10 bp helical twist of DNA constrain a single TF binding domain to access the major groove over stretches of DNA <10 bp. TFBSs with >10 bp binding sites are typically due to homo- or hetero-multimers, or to TFs with >1 DNA binding domain. To answer your question directly, using ~400 TFBS that are literature curated from small-scale studies (e.g no ChIP-seq or Chip-chip) based on DNAse footprinting, gel shift, etc. in the ORegAnno database, leads to an estimate of 11.9 bp. A quick double check of this value would be appreciated.

[Khader Shameer]

Thanks a lot Casey !

Answer 2

[Jelena Aleksic]

The length of DNA binding sites of individual transcription factors tends to be in the region of 6-10 bp, and that doesn't very all that much between say fly and human, as a lot of the TF DNA binding domains are highly conserved. The length will vary depending on the specific transcription factor family you're looking at - for some of them, X-ray crystallography structures have been published, you can look these up for binding site lengths. Motifs aren't necessarily a true reflection of the exact length of binding sites, as they are computationally derived from the sequence, rather than experimentally determined.