Noncoding Transcription at Enhancers: General Principles and Functional Models

G. Natoli and J.C. Andrau, Noncoding Transcription at Enhancers: General Principles and Functional Models, Annual Review of Genetics, 2012

The enhancer-associated transcripts were detected in areas devoid of H3K4me3 and most were bidirectional, relatively short, and nonpolyadenylated. These bidirectional transcripts were indicated as eRNAs. However, because enhancer-templates RNAs can frequently be unidirectional, such as in the case of Hgh and glob in genes, hereinafter we refer to 1d-eRNAs and 2d-eRNAs to indicate unidirectional and bidirectional eRNAs, respectively.

The current views on the biological role of enhancer transcription, each supported by different types of evidence, can be grouped as follows:

  1. Enhancer transcription is due to the unavoidable, random collisions of Pol II with open and accessible chromatin; as such, it represents noise only and does not carry out any biological function.
  2. Functional effects of enhancer transcription are due to the transcription process, specifically, to the movement along the chromatin template of Pol II and its associated enzymatic activities, such as histone acetyltransferases and chromatin-remodeling complexes.
  3. Enhancer-templated RNAs are functional molecules involved in transcriptional control either locally (cis activity) or at distant locations (trans activity)

A recent genome-wide analysis of three-dimensional interactions mediated by RNA Pol II indicated that RNA Pol II-dependent cell-type-specific spatial interactions between enhancers and promoters are a very common occurrence. These data imply that interacting enhancers and promoters may undergo coordinated transcription in the same nuclear compartments (transcription factories). In this light, it is tempting to speculate that RNA Pol II recruitment to a given enhancer may be exploited to promote its recruitment to transcription factories where the cognate gene is also transcribed, thus favoring spatial proximity and increasing the chances of productive contracts.

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