Gene regulation gets more complicated: Many promoters may also be enhancers

By examining how a family of non-coding RNAs affects gene expression, Broad researchers and colleagues have stumbled across evidence that gene-regulating promoters and enhancers may be two sides of the same coin.

Lauren Solomon, Broad Communications
Credit: Lauren Solomon, Broad Communications

According to the conventional wisdom, gene expression is controlled by two separate types of elements: promoters (from which transcription begins) and enhancers (regulatory DNA sequences positioned at some distance from promoters).  A new study reported by Broad researchers and colleagues in the journal Nature, however, shows that this distinction may be an artificial one, and that the non-coding genome may hide regulatory signals in unexpected places.

The team — led by postdoctoral fellow Jesse Engreitz and Broad founding director Eric Lander — set out to study whether many long non-coding RNAs (lncRNAs, some of which help control gene expression) influence neighboring genes, information that could help reveal why the genome is sprinkled with tens of thousands of these elements.

They were surprised to find that in many cases the promoters of the lncRNAs’ genes — but not the lncRNAs themselves — affected nearby gene activity. Put another way: the promoters for one gene acted as an enhancer for another.

Even more surprisingly, they found that this effect was not limited to lncRNA genes. Indeed, the promoters of many protein-coding genes also acted as regulators of neighboring genes’ expression.

These discoveries suggest that the promoter one gene may regulate the expression of others — showing that the expression of neighboring genes is interconnected.

The team’s findings highlight complex crosstalk that can involve many types of signals. Understanding this crosstalk may help explain how cells shape their gene expression programs, and also help interpret genetic variation in the non-coding regions of the genome.


Paper(s) cited

Engreitz JM, et alLocal regulation of gene expression by lncRNA promoters, transcription and splicing. Nature. Online October 26, 2016. DOI: doi:10.1038/nature20149.