Creative Minds: Building the RNA Toolbox

Mice

Caption: Genetically identical mice. The Agouti gene is active in the yellow mouse and inactive in the brown mouse.
Credit: Dana Dolinoy, University of Michigan, Ann Arbor, and Randy Jirtle, Duke University, Durham, NC

Step inside the lab of Dana Dolinoy at the University of Michigan, Ann Arbor, and you’re sure to hear conversations that include the rather strange word “agouti” (uh-goo-tee). In this context, it’s a name given to a strain of laboratory mice that arose decades ago from a random mutation in the Agouti gene, which is normally expressed only transiently in hair follicles. The mutation causes the gene to be turned on, or expressed, continuously in all cell types, producing mice that are yellow, obese, and unusually prone to developing diabetes and cancer. As it turns out, these mutant mice and the gene they have pointed to are more valuable than ever today because they offer Dolinoy and other researchers an excellent model for studying the rapidly emerging field of epigenomics.

The genome of the mouse, just as for the human, is the complete DNA instruction book; it contains the coding information for building the proteins that carry out a variety of functions in a cell. But modifications to the DNA determine its function, and these are collectively referred to as the epigenome. The epigenome is made up of chemical tags and proteins that can attach to the DNA and direct such actions as turning genes on or off, thereby controlling the production of proteins in particular cells. These tags have different patterns in each cell type, helping to explain, for example, why a kidney and a skin cell can behave so differently when they share the same DNA.

Some types of genes, including Agouti, are particularly vulnerable to epigenomic effects. In fact, Dolinoy has discovered that exposing normal, wild-type (brown) mice to certain chemicals and dietary factors during pregnancy can switch on the Agouti gene in their developing offspring, turning their coats yellow and their health poor. Dolinoy says these experiments raise much larger questions: If researchers discover populations of humans that have been exposed to lifestyle or environmental factors that modify their epigenomes in ways that may possibly contribute to risk for certain diseases, can the modification be passed on to their children and grandchildren (referred to as transgenerational epigenetic inheritance, a controversial topic)? If so, how can we develop the high-precision tools needed to better understand and perhaps even reduce such risks? The University of Michigan researcher received a 2015 NIH Director’s Transformative Research Award to undertake that challenge.

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Largest Study Yet Shows Mother’s Smoking Changes Baby’s Epigenome

Pregnant woman smoking

Credit: Daniel Berehulak/Getty Images

Despite years of public health campaigns warning of the dangers of smoking when pregnant, many women are unaware of the risk or find themselves unable to quit. As a result, far too many babies are still being exposed in the womb to toxins that enter their mothers’ bloodstreams when they inhale cigarette smoke. Among the many infant and child health problems that have been linked to maternal smoking are premature birth, low birth weight, asthma, reduced lung function, sudden infant death syndrome (SIDS), and cleft lip and/or palate.

Now, a large international study involving NIH-supported researchers provides a biological mechanism that may explain how exposure to cigarette toxins during fetal development can produce these health problems [1]. That evidence centers on the impact of the toxins on the epigenome of the infant’s body tissues. The epigenome refers to chemical modifications of DNA (particularly methylation of cytosines), as well as proteins that bind to DNA and affect its function. The genome of an individual is the same in all cells of their body, but the epigenome determines whether genes are turned on or off in particular cells. The study found significant differences between the epigenetic patterns of babies born to women who smoked during pregnancy and those born to non-smokers, with many of the differences affecting genes known to play key roles in the development of the lungs, face, and nervous system.

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Charting the Chemical Choreography of Brain Development

Drawing of baby, adolescent, and adult with decorative brains

Credit: Image courtesy of Scot Nicholls

Once in a while a research publication reveals an entirely new perspective on a fundamental issue in biology or medicine. Today’s blog is about such a paper. The story, though complex, is very significant.

The choreography of human brain development is amazing, but quite mysterious. Today’s post highlights a study [1] that reveals the locations of some of the chemical choreographers that collaborate with DNA to orchestrate these fancy moves in the brain. Continue reading