The best definition to Enhancer and Promoter?

Question

[Shicheng Guo]

Is there any deep discussion about the best definition to enhance and promoter?

Currently, In my views, promoter is the region from -4000 to +1000 while enhance is -20000 to -4000.

Is there any discuss to such problem? Is there any best definition to promoter and enhance?

chr1    49090   65090   NM_001005484    OR4F5   +       Enhancer        69090
chr1    65090   70090   NM_001005484    OR4F5   +       Promoter        69090
chr1    69090   69090   NM_001005484    OR4F5   +       UTR5    69090
chr1    69090   70008   NM_001005484    OR4F5   +       Exon1   69090
chr1    70008   70008   NM_001005484    OR4F5   +       UTR3    69090
chr1    70008   72008   NM_001005484    OR4F5   +       Downstream      69090
chr1    347658  363658  NM_001005221    OR4F29  +       Enhancer        367658
chr1    363658  368658  NM_001005221    OR4F29  +       Promoter        367658
chr1    367658  367658  NM_001005221    OR4F29  +       UTR5    367658
chr1    367658  368595  NM_001005221    OR4F29  +       Exon1   367658
chr1    368595  368595  NM_001005221    OR4F29  +       UTR3    367658
chr1    368595  370595  NM_001005221    OR4F29  +       Downstream      367658
chr1    347658  363658  NM_001005224    OR4F3   +       Enhancer        367658
chr1    363658  368658  NM_001005224    OR4F3   +       Promoter        367658

[zizigolu]

perhaps in your special case the region containing enhancer and promoter is overlap

Answer 1

[Istvan Albert]

I would always be cautious to define biological concepts in terms of linear coordinates, the cutoffs are very "human understanding" oriented round numbers that won't generalize well.

When in doubt of what a term means consult the Sequence Ontology:

Enhancer: http://www.sequenceontology.org/browser/current_svn/term/SO:0000165

Promoter: http://www.sequenceontology.org/browser/current_svn/term/SO:0000167

[Fidel]

I didn't know about the sequenceontology.org although apparently has been up since 2009.

Answer 2

[cyril-cros]

An enhancer does not even have to be on the same chromosome (see http://www.ncbi.nlm.nih.gov/pubmed/16873069) for an example on the monoallelic choice of olfactory receptor WARNING the article had some conclusions invalidated), and can be upstream, downstream, up to 1Mbp away. A promoter is typically in the near cis region of your gene.

The fundamental idea is that RNA polymerase subunits are recruited (or blocked) by a multitude of transcription factors, which can bind to enhancers or promoters, forming a 'mediator complex'.

[Emily]

I think there is actually a TF/enhancer-interaction protein complex called 'mediator complex'.

[cyril-cros]

You are absolutely correct, the mediator complex is something else. A better term would be 'transcription initiation complex'.

Answer 3

[Anima Mundi]

Hello, I give you my personal understanding of those concepts. A promoter is the nearest in cis discrete region allowing for (promoting the) expression of a given gene. Any other discrete sequence enhancing the expression of one or more genes is an enhancer (normally, but not necessarily, in cis). More general term is regulatory element, comprising any sequence having any kind of effect on the transcription of the gene. Regulatory elements can be cis-acting (e.g. locus control region,LCR) or trans-acting (or, sometimes, both).

[PoGibas]

Would agree with that:

A promoter is the nearest (to TSS) in cis discrete region allowing for (promoting the) expression of a given gene (or genes). Any other discrete sequence (region) enhancing the expression of one or more genes is an enhancer (normally, but not necessarily, in cis). :-)

[Anima Mundi]

Good specifications, 100% agree!

Answer 4

[Ryan Dale]

As the other answers point out, a genomic distance approach is not useful to define enhancers. A more rigorous definition of enhancers might integrate multiple data sources. For example:

• Identify regions interacting with promoters in long-range interaction experiments (e.g., Schoenfelder et al. 2015)
• Since these interactions could be activating, repressive, or nonfunctional, select candidate regions that have enhancer-like chromatin modifications (e.g., from genome segmentation algorithms like ChromHMM)
• Merge those regions, or cross-reference to see the quality of predictions, with functional assays like those reported in the VISTA enhancer browser
• For the genes you really care about, you would need to experimentally disrupt the candidate enhancer (e.g. with CRISPR) to see if the candidate region is required for transcription. But even if you get a negative result, it's still possible there are other redundant enhancers, in which case you'd have to disrupt them all!

As for "promoter" definition, it may depend on your question: If you're looking at PolII recruitment, you might benefit from extending the promoter region downstream into the transcript, while focusing upstream would be useful for TF binding. For histone modifications it probably depends on the particular modification.