Enhancer RNAs alter gene expression: New class of molecules may be key emerging 'enhancer therapy'

June 4, 2013 by Scott Lafee, University of California - San Diego

(Medical Xpress)—In a pair of distinct but complementary papers, researchers at the University of California, San Diego School of Medicine and colleagues illuminate the functional importance of a relatively new class of RNA molecules. The work, published online this week in the journal Nature, suggests modulation of "enhancer-directed RNAs" or "eRNAs" could provide a new way to alter gene expression in living cells, perhaps affecting the development or pathology of many diseases.

Enhancers are sequences in the that act to boost or "enhance" the activity or expression of nearby genes. They "often behave in a cell-specific manner and play an important role in establishing a cell's identity and functional potential," said Christopher Glass, MD, PhD, a professor in the department of Medicine and Cellular and at UC San Diego and principal investigator of one of the papers.

Although enhancers have been recognized for more than 25 years, scientists have labored to fully flesh out the breadth and complexity of what enhancers do and how they do it. In 2010, it was discovered that enhancers directed expression of on a broad scale in and , a type of immune system cell. Dubbed eRNAs, they were different from other classes of nuclear non-coding RNAs, and raised new questions about their potential roles in the functions of enhancers. The two Nature papers attempt to answer some of these questions.

In the first, principal investigator Glass and colleagues investigated a pair of related transcriptional repressors called Rev-Erb-alpha and Rev-Erb-beta (proteins with important roles in regulating the circadian rhythm in many cell types) in mouse macrophages. Using genome-wide approaches, they found that the Rev-Erb proteins repressed in macrophages primarily by binding to enhancers. Collaboration with researchers at the Salk Institute for Biological Studies revealed that the repressive function of Rev-Erbs was highly correlated with their ability to repress the production of eRNAs.

In the second paper, principal investigator Michael G. Rosenfeld, MD, a professor in the UC San Diego Department of Medicine and Howard Hughes Medical Institute investigator, and colleagues looked at estrogen receptor binding in human breast cancer cells – and its impact on enhancer transcription. In contrast to the repressive functions of Rev-Erbs, estrogen receptors (ERs) activate gene expression; but, like Rev-Erbs, they primarily function by also binding to enhancers. ER binding was shown to be associated with increases in enhancer-directed eRNAs in the vicinity of estrogen-induced genes, and to exert roles on activation of coding target genes.

Both papers offer new evidence that eRNAs significantly contribute to enhancer activity, and therefore to expression of nearby genes. "Because many broadly expressed genes that play key roles in essential cellular functions are under the control of cell-specific , the ability to affect enhancer function by knocking down eRNAs could potentially provide a new strategy for altering gene expression in vivo in a cell-specific manner," said Glass, noting that in his research, anti-sense oligonucleotides were developed in conjunction with Isis Pharmaceuticals, which suppressed enhancer activity and reduced expression in nearby genes.

Explore further: Genetic master controls expose cancers' Achilles' heel

Related Stories

Genetic master controls expose cancers' Achilles' heel

April 11, 2013
In a surprising finding that helps explain fundamental behaviors of normal and diseased cells, Whitehead Institute scientists have discovered a set of powerful gene regulators dubbed "super-enhancers" that control cell state ...

Genome-wide atlas of gene enhancers in the brain online

January 31, 2013
Future research into the underlying causes of neurological disorders such as autism, epilepsy and schizophrenia, should greatly benefit from a first-of-its-kind atlas of gene-enhancers in the cerebrum (telencephalon). This ...

Coordinating the circadian clock: Researchers find that molecular pair controls time-keeping and fat metabolism

April 4, 2012
(PhysOrg.com) -- The 24-hour internal clock controls many aspects of human behavior and physiology, including sleep, blood pressure, and metabolism. Disruption in circadian rhythms leads to increased incidence of many diseases, ...

Recommended for you

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.