Promoter-proximal elements are binding sites for transcription factors, found approximately 200 base pairs before the transcription start site (TSS). It is possible for a single gene to have multiple promoter-proximal elements, allowing multiple transcription factors to act on a single gene. This allows a range of transcriptional activities to be obtained (instead of a gene either being ‘on’ or ‘off’).
Distal enhancers are distant regulatory elements that are much more difficult to identify. Also interacting with transcription factors, they can be kilobases away from the TSS, and be found in introns. Enhancer trapping can be used to identify distal enhancers. This is done by randomly inserting a reporter gene to create a mutant library, and studying its expression. Where the reporter is upregulated, the interactions between the insertion site (of the reporter gene) and the enhancer are studied, attempting to identify the cause of the upregulation. This can be done by cloning and sequencing.