Scientists at the Research Institute of Molecular Pathology (IMP) in Vienna uncover basic mechanisms of action for hormones.
Thousands of regulatory regions on the genomic DNA determine which part of a cell’s genetic information is expressed and which is silent. Daria Shlyueva and Alexander Stark from the IMP in Vienna analysed such control-regions and the changes in activity that follow treatment with a hormone.
They showed that - depending on the cell type - a single hormone can influence different regions. The findings are published in the advance online edition of the journal Molecular Cell this week.
The entire information for the development and functioning of an organism is encoded in its DNA. Genes contain the building plans for the molecules that constitute living beings. However, not all genes are active at all times, allowing the various cell types and organs to perform specific functions.
This diversity is precisely regulated by non-coding regulatory regions in the genomic DNA. Alexander Stark, a biochemist and Group Leader at the IMP, is interested in finding out how these regions act as “molecular switches” to turn genes on or off at the right time.
In 2013, the Stark group developed STARR-Seq, a novel technique to screen entire genomes for certain control regions of gene expression, so-called enhancers, and to measure their activity. Now they took this method one step further. “We were always interested in finding out what characterises a DNA-sequence that performs regulatory functions”, he explains. “Now we wanted to go into more detail and show that STARR-Seq can identify hormone-dependent regulators and measure them.“
Daria Shlyueva, a PhD student in the Stark group, cultivated two different cell types of the fruit fly and exposed them to the steroid hormone ecdysone. By comparing enhancer activities along the entire genomes of treated and untreated cells, the scientists were able to show that a single hormone can regulate different enhancers in different cells and can influence the activity of genes either positively or negatively.
The hormone’s receptor in the cell nucleus and further binding-partners, so-called transcription factors, determine which region of the DNA is influenced. The combination of these interacting molecules is responsible for the variable responses in different tissues and at different stages of development. These findings explain how regulatory regions of DNA can combine input from the cell’s environment with cell type-specific information to trigger a whole range of reactions.
Searching for hormone-dependent DNA-elements in humans
Steroid hormones such as estrogen or testosterone have important functions in humans. Researchers in the lab of Alexander Stark have therefore started to look for molecular switches in the human genome. “In the future, our system could be used to identify control regions on DNA that are regulated by human hormones”, says Stark. “This would be another important step towards potential medical applications.”
D. Shlyueva, C. Stelzer, D. Gerlach, J.O. Yánez-Cuna, M. Rath, L.M. Boryn, C.D. Arnold and A. Stark: Hormone-responsive enhancer activity maps reveal predictive motifs, indirect repression and targeting of closed chromatin. Mol. Cell, online Early Edition, 27 March 2014 (doi/10.1016/j.molcel.2014.02.026).
The Stark Group is supported by the Austrian Science Fund (FWF) and a Starting Grant from the European Research Council (ERC). Basic research at the IMP is supported by Boehringer Ingelheim. Find out more about research in the Stark-lab: www.imp.ac.at/research/research-groups/stark-group/
An illustration to be used free of charge in connection with this press release can be downloaded from the IMP website: www.imp.ac.at/pressefoto-Ecdyson
About Alexander Stark
Alexander Stark joined the IMP as Group Leader in October 2008. Prior to his current position he was a postdoctoral fellow at the Broad Institute of MIT and Harvard and at CSAIL MIT. Stark studied biochemistry at the University of Tübingen and received his PhD from the EMBL in Heidelberg and the University of Cologne. In 2009, Alexander Stark was awarded a Starting Grant by the European Research Council ERC. In 2012, he was accepted into the “EMBO Young Investigator Programme“.
About the IMP
The Research Institute of Molecular Pathology (IMP) in Vienna is a basic biomedical research institute largely sponsored by Boehringer Ingelheim. With over 200 scientists from 37 nations, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. Research areas include cell and molecular biology, neurobiology, disease mechanisms and computational biology.
Dr. Heidemarie Hurtl | idw - Informationsdienst Wissenschaft
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences