Transcription Factors are the ones that determine firstly the activity of enhancers.  In fact, they can bind enhancer DNA sequence before these enhancer are actually active. Active marks such as production enhancer RNA and the presence of h3k27ac, or h3k9ac, or h3k18ac (that are all marks of active regions) rise after the binding of transcription factors binding. Transcription factors usually couple with co-activators such as CBPA or p300 that are actually histone acetyltransferases. They deposit the acetyl mark, that is a positive charge, will allow the chromatin to become more open and allow the binding of RNA pol2/mediator/integrator complex to these open enhancer region. This huge complex will form and stabilize the 3D loop formed between the enhancer and the targeted gene, promoting the massive transcription of this exact gene. This model has been challenged by a science paper showing that enhancer RNA is temporarily the first sign that enhancer is active, even before acetylation marks are deposited. Still is under debate but my feeling depends case by case and related to which method you perform to detect enhancer RNA presence.

http://www.nature.com/ng/journal/v45/n10/full/ng.2746.html

http://genome.cshlp.org/cgi/pmidlookup?view=long&pmid=25391375

Specific function of expression

Chromatin state, levels of transcription factor proteins in the cell, and several other factors such as levels of nucleotides influence transcription.  But producing more transcription factor to "turn on" a gene is slow, so most transcription factor complexes have at least a few proteins that are activated and deactivated by modifications such as phosphorylation.  If you look up G-protein coupled receptors and kinases you will find that this is a huge and complex family of regulatory proteins that respond to stimuli and modulate the transcription of genes, and other activities in the cell.

IN addition to looking at chromatin state as mentioned by Sandip Rath,  you can also look at the amount of transcription at enhancer loci using CAGE for example.

As said before, active enhancers usually possess distinctive epigenetic marks, being laid on DNA and histone proteins, but not defined by sequence. Most commonly studied are H3K4me1, defining "primed" enhancers (DNA sequences which are marked to be enhancers) and H3K27ac which marks active DNA sequences (enhancers, in combination with the former, or promoters in combination with H3K4me3). You can also find DNA hydroxymethylation (5hmC) in some active enhancers.

Active enhancers can also be recognized by their transcription level (as mentioned above) and the transcription of so-called eRNA (enhancer RNA) which seem to stimulate the activity of enhancers. Active enhancers are, in contrary to what was written above, also characterized by a high level of TF binding, which can be used to define "super-enhancers" (see Whyte et al., 2013 and Loven et al., 2013 in Cell). These SE are instrumental in differentiation processes and have an even higher level of activity. The current hypothesis is that TF cooperate to make "bridges" and loops between enhancers and promoters to put together a highly active transcriptional complex.

There is a growing body of publications showing how enhancers are primed, activated and then repressed and even erased during differentiation (see Lara-Astasio et al., 2015 in Science for a good example in the hematopoietic lineages), and what marks are associated with such changes.

Transcription Factors are the ones that determine firstly the activity of enhancers.  In fact, they can bind enhancer DNA sequence before these enhancer are actually active. Active marks such as production enhancer RNA and the presence of h3k27ac, or h3k9ac, or h3k18ac (that are all marks of active regions) rise after the binding of transcription factors binding. Transcription factors usually couple with co-activators such as CBPA or p300 that are actually histone acetyltransferases. They deposit the acetyl mark, that is a positive charge, will allow the chromatin to become more open and allow the binding of RNA pol2/mediator/integrator complex to these open enhancer region. This huge complex will form and stabilize the 3D loop formed between the enhancer and the targeted gene, promoting the massive transcription of this exact gene. This model has been challenged by a science paper showing that enhancer RNA is temporarily the first sign that enhancer is active, even before acetylation marks are deposited. Still is under debate but my feeling depends case by case and related to which method you perform to detect enhancer RNA presence.

http://www.nature.com/ng/journal/v45/n10/full/ng.2746.html

http://genome.cshlp.org/cgi/pmidlookup?view=long&pmid=25391375

the active enhancers usually are identified as H3K27ac positive,H3K4me1 positive and sometimes with eRNA.

Excellent responses guys! Thanks very much for sharing your insights. helps a lot :)

The activity of enhancers is determined by a combination of factors. Transcription factors being probably the most important. However, it is well documented that the same transcription factors have very different binding sites in different cell types. There are two factors that might explain the different binding sites - first, different interaction partners - second, different chromatin accessibility that determines which sites are accessible to transcription factors. That brings along the question what opens up the specific regions in cells? Ken Zaret has propagated the idea of so called pioneer transcription factors that can access DNA even in the nucleosomal contact. These factors are believed to initiate the activation of enhancer, followed by recruitment of other factors such as coactivators (p300), chromatin remodelers, histone modifiers, other transcription factors, polymerase II etc. To experimentally determine an active enhancer it usually has, as stated before, H3K4me1and H3K27ac modifications and p300 binding.