A new study, published in the journal Genome Research by researchers at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James), provides the first evidence that cells can regulate many genes at once by looping their DNA, contributing to cancer when it goes awry. In this study, the gene regulation was discovered in breast cancer cells as a response to the hormone estrogen and resulted in the silencing of 14 genes at one time.
Tim H.-M. Huang, professor of molecular virology, immunology and medical genetics in the OSUCCC-James human cancer genetics program, and Pei-Yin Hsu, a visiting scholar and researcher in Huang’s lab, discovered the DNA looping event in a breast cancer cell line gene cluster at chromosome region 16p11.2. They validated the finding using normal human breast epithelial cells and two animal models.
In addition, they used the normal-cell model to determine if long-term exposure to nine estrogen-like chemicals can initiate gene silencing through this mechanism. These chemicals included diethylstilbestrol, two thalates and bisphenol A (BPA).
The suppressive effects varied in normal cells. When the investigators exposed a group of four rats to BPA for 21 days, however, they found concurrent suppression of ten genes comparable to those located at 16p11.2. These findings, says Huang, suggest that continuous exposure to estrogen-like compounds might lead to permanent silencing of genes located in this conserved cluster.
In healthy breast epithelial cells, 14 gene regulatory sites came together to form a single, temporary transcription site, Huang says. “But in breast cancer cells, there is no coordinated transcription site pairing, the DNA loops become tangled and the entire gene complex shuts down in a dead knot.” (For a demonstration of DNA looping, click here.)
In some cases, Huang says, this multi-gene regulatory mechanism can increase gene expression and oncogenic activity, and further contribute to cancer development.
“We offer a new concept in this paper for the collective regulation of gene transcription,” says first author Hsu, who identified the loop structures and their significance. “We found that in normal breast cells, DNA looping is more flexible and brings different promoters together temporarily. But in cancer, this complex just locks up and causes long-term suppression.”
Researchers generally believe that transcription factors bind to a site on a single gene, and then the gene is actively transcribed, according to Huang. The study’s findings show that this is not always the case. Sometimes the promoter is located far away, and it is remotely controlled.
"Overall, our study shows that certain regions of the genome are silenced because the DNA has lost flexibility, and that this inflexible DNA status might be a good marker for studying environmental exposure to estrogen-like compounds,” Hsu says.
Funding from the National Institute of Environmental Health Sciences and the National Cancer Institute supported this research.
Other researchers involved in this study were Hang-Kai Hsu, Gregory A.C. Singer, Pearlly S. Yan, Benjamin A.T. Rodriguez, Joseph C. Liu, Yu-I Weng, Daniel E. Deatherage, Zhong Chen and Qianben Wang of OSUCCC-James; Julia S. Pereira, Ricardo Lopez, and Jose Russo of Fox Chase Cancer Center; Coral A. Lamartiniere of the University of Alabama at Birmingham; and Kenneth P. Nephew of Indiana University.
The Ohio State University Comprehensive Cancer Center- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (http://cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top 20 cancer hospitals in the nation, The James is the 180-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC-James is one of only seven funded programs in the country approved by the NCI to conduct both Phase I and Phase II clinical trials.
Darrell E. Ward | EurekAlert!
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
21.08.2017 | Materials Sciences
21.08.2017 | Health and Medicine
21.08.2017 | Materials Sciences