Nav: Home

In fruit fly and human genetics, timing is everything

May 25, 2017

CHAPEL HILL, NC - Every animal starts as a clump of cells, which over time multiply and mature into many different types of cells, tissues, and organs. This is fundamental biology. Yet, the details of this process remain largely mysterious. Now, scientists at the University of North Carolina at Chapel Hill have begun to unravel an important part of that mystery.

Using the fruit fly Drosophila, a standard lab model for studying animal biology, the researchers discovered a cascade of molecular signals that program gene activity to drive the fly from one stage of maturation to the next, like a baby turning into an adult. Part of this programming, they found, involves alterations to the way DNA is packaged. Those alterations open up certain regions of DNA to allow gene activity and close off other regions to prevent gene activity. The scientists found evidence that these changes to DNA accessibility occur in sequence.

"We're finally getting at one of the core mechanisms in biology, which determine the timing and sequence of events in normal animal development at the level of our genes," said Daniel J. McKay, PhD, assistant professor of genetics at the UNC School of Medicine and biology at the UNC College of Arts and Sciences.

This basic biology finding could have significance for human health, too. The changes to cell reprogramming that the scientists observed in the young flies can occur inappropriately in adult human cells - spurring cancer, for example.

"We hope that this work will help us better understand what goes awry in cancer and other diseases," McKay said.

In the study, published in Genes & Development, McKay and colleagues began by examining the molecular impact of the fruit fly hormone ecdysone, which causes a young insect to shed its old form and adopt a new one as it moves toward maturity.

Scientists know that ecdysone binds to a receptor, EcR, in the nuclei of cells throughout the bodies of insects. EcR is a transcription factor, a genetic master switch. When bound by ecdysone, it turns on a particular set of genes. And those genes, in turn, are involved in the development of proteins - the machines of biology.

Analyzing Drosophila wing cells, McKay and colleagues found evidence that wing development occurs via a cascade of these changes in gene activity.

"We found first-tier genes that respond immediately to ecdysone, and then they - together with EcR - activate a second tier of genes, and then these two tiers of genes, operating in concert, act on a third tier," said McKay. "So we observed these waves of changes in gene expression that drive the development of wing tissue."

Using genome-wide sequencing technologies, McKay's team found that these changes in gene expression are associated with changes in the way DNA is "packaged."

DNA is looped around support proteins called histones, and this histone-DNA combination is called chromatin.

When chromatin is relatively loose and open, genes can become active. When chromatin is tight and closed, genes are mostly silenced. McKay and colleagues found that ecdysone activates some genes to produce special transcription factor proteins that open or close chromatin. This altering of chromatin represents a fundamental reprogramming of cells.

McKay and colleagues had shown in prior work that the pattern of chromatin accessibility in the fruit fly appears to change significantly over the course of development but can be very similar at any given time across fly tissues.

To the scientists, these findings collectively suggest that changes in chromatin leads to cascades of gene activity that drive fly development. That is, chromatin changes - over time - would help enforce the timing of the various processes underway during biological development. And these changes represent an important developmental mechanism, one that is likely at work in humans.

McKay and his team plan further research to study how these cascades of changing chromatin accessibility and gene activity differ from one part of the fly to another.

As McKay notes, this area of investigation could have relevance beyond developmental biology. The expression of growth and survival genes is normal during early biological development - when we're young. But cancerous cells, for example, use those genes to sustain runaway proliferation to cause disease.

Therefore, understanding the molecular factors that open or close chromatin - and allow or shut down the activity of these powerful genes - may give biologists a better picture of how cancers arise. Armed with that knowledge, scientists could try to create more precise weapons with which to fight cancer cells.
-end-
The study's lead authors were UNC graduate students Christopher M. Uyehara and Spencer L. Nystrom. Other co-authors were Matthew J. Niederhuber, Mary Leatham-Jensen, as well as Yiqin Ma and Laura A. Buttitta, from the University of Michigan.

This work was supported by funds from the UNC School of Medicine, the UNC College of Arts and Sciences, and the Integrative Program for Biological and Genome Sciences (iBGS).

University of North Carolina Health Care

Related Dna Articles:

Penn State DNA ladders: Inexpensive molecular rulers for DNA research
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
It is easier for a DNA knot...
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
How do metals interact with DNA?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
Electrons use DNA like a wire for signaling DNA replication
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
Switched-on DNA
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Researchers are first to see DNA 'blink'
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
Finding our way around DNA
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
A 'strand' of DNA as never before
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
Doubling down on DNA
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
'Poring over' DNA
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.

Related Dna Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...