Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

How Genes Tell Cellular Construction Crews, “Read Me Now!”

Published: Thursday, August 15, 2013
Last Updated: Thursday, August 15, 2013
Bookmark and Share
Stowers researchers show that DNA sequences at the beginning of genes—at least in fruit flies— contain more information than previously thought.

When egg and sperm combine, the new embryo bustles with activity. Its cells multiply so rapidly they largely ignore their DNA, other than to copy it and to read just a few essential genes. The embryonic cells mainly rely on molecular instructions placed in the egg by its mother in the form of RNA.

The cells translate these RNA molecules into proteins that manage almost everything in the first minutes or hours of the embryo's life. Then, during the so-called midblastula transition, cells start transcribing massive amounts of their own DNA. How embryonic cells prepare for this moment, and how they flag a small set of genes for transcription before that, holds important information about normal development and disease in animals and in humans.

A new study that sheds light on these questions appears in the Aug. 13 issue of eLife Sciences, authored by researchers at the Stowers Institute for Medical Research. The team, led by Associate Investigator Julia Zeitlinger, Ph.D., shows that in the fruit fly Drosophila melanogaster, genes active in the first two hours of a fertilized egg are read quickly due to special instructions at the beginning of each gene, in a region aptly named the “promoter.”

Within each promoter region, different combinations of short control elements or “boxes” form a code that instructs specialized construction crews, called RNA polymerases, where and when to start transcribing. Researchers long thought that once an RNA polymerase appears at the worksite it would quickly finish the job.

“The most important result is that promoters are different,” Zeitlinger says. “The general paradigm for a long time has been a promoter is a promoter. But really what we see is that they have different functions.”

As a postdoctoral fellow at MIT, Zeitlinger unexpectedly discovered that sometimes RNA polymerase II pauses at the beginning of a gene as if taking a lunch break. More often than not, pausing occurred at genes important for development. Zeitlinger thought pausing may help get these molecular construction workers on site before a huge work order is due.

“We were wondering whether pausing was being used for preparing global gene activation during the midblastula transition,” says Kai Chen, PhD, a former graduate student in Zeitlinger’s lab and the study’s first author.  “We expected to see widespread pausing before that transition.”

The fruit fly Drosophila melanogaster was a perfect test subject. This fly embryo takes two hours to reach the midblastula transition providing plenty of time to analyze what happens during this early period. Furthermore, decades of previous research on the flies provided context to guide the work.

Chen used a method called ChIP-seq, which can locate RNA polymerase II molecules on any gene. Paused polymerases would show up only at the beginning of genes. Working polymerases, on the other hand, would be found throughout the gene body.

The results took the Stowers team by surprise. Before the midblastula transition, RNA Polymerase II appeared to rarely pause as it transcribed roughly 100 early genes. And no construction crews were sitting idle on inactive genes in preparation for the midblastula transition. Pausing only became widespread only during the midblastula transition itself.

“What we found was not what we expected at all,” Zeitlinger says. Before the midblastula transition, instead of preparing for a huge workload the construction crews were busy completing rush jobs. “The polymerase has to come to the promoter and immediately transcribe because there's so little time to do the job. That's one way of making transcription faster. ”

When Chen and colleagues computationally compared the DNA sequences of promoters where pausing occurred with those where it didn't, a pattern emerged. They found that three different types of promoters correlated with the construction crew's pausing behavior.

The genes that RNA Polymerase II reads before the midblastula transition were often preceded by a promoter that seemed to yell, “Urgent! Don't even think about pausing.” These promoters contain what’s known as a TATA-box, named for its conserved arrangement of nucleotides, most commonly TATAA.

As cell division slows down during the midblastula transition, cells have the luxury of pausing, perhaps to fine-tune when transcription begins, Zeitlinger says.

These midblastula genes were regulated by promoters that contain a variety of specific promoter elements associated with paused RNA polymerase, including GAGA, Downstream Promoter Element (DPE), Motif Two Element (MTF) and Pause Button (PB).

The team also found a third type of promoter, which contained both the TATA-box and the pausing sequences. At these genes, RNA polymerase II does not pause initially but begins to pause during the midblastula transition.

Zeitlinger hopes learning more about promoters will give clues to the functions of unknown genes. Because these promoter sequences are not specific to flies, the differences among promoter types may be conserved in other animals as well.

“My lab is interested in understanding how development or even diseases are encoded in the genome,” Zeitlinger says. “If we understand transcription, then we can predict a lot of what genomes encode, in terms of disease or differences between individuals.”

“Promoters had been seen by some scientists as sort of boring,” she adds, “but now, they are starting to get really interesting.”

Other contributors include Jeff Johnston, Wanqing Shao, Samuel Meier and Cynthia Staber, all from the Stowers Institute.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Ancient Vertebrate Uses Familiar Tools
Sea lamprey studies show remarkably conserved gene expression patterns in jawless versus jawed vertebrates.
Monday, September 15, 2014
Repressing the Repressors May Drive Tissue-Specific Cancers
Stowers scientists establish Drosophila and mammalian models to study mutations found in pediatric brain tumors.
Friday, August 29, 2014
Scientific News
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Watching a Tumour Grow in Real-Time
Researchers from the University of Freiburg have gained new insight into the phases of breast cancer growth.
Childhood Cancer Cells Drain Immune System’s Batteries
Cancer cells in neuroblastoma contain a molecule that breaks down a key energy source for the body’s immune cells, leaving them too physically drained to fight the disease.
Urine Proteins Point to Early-Stage Pancreatic Cancer
A combination of three proteins found at high levels in urine can accurately detect early-stage pancreatic cancer, researchers at the BCI have shown.
Researcher Discovers Trigger of Deadly Melanoma
New research sheds light on the precise trigger that causes melanoma cancer cells to transform from non-invasive cells to invasive killer agents, pinpointing the precise place in the process where "traveling" cancer turns lethal.
Genetic Tug of War
Researchers have reported on a version of genetic parental control in mice that is more targeted, and subtle than canonical imprinting.
Error Correction Mechanism in Cell Division
Cell biologists have reported an advance in understanding the workings of an error correction mechanism that helps cells detect and correct mistakes in cell division early enough to prevent chromosome mis-segregation and aneuploidy, that is, having too many or too few chromosomes.
How to Become a Follicular T Helper Cell
Uncovering the signals that govern the fate of T helper cells is a big step toward improved vaccine design.
Researchers Resurrect Ancient Viruses
Researchers at Massachusetts Eye and Ear and Schepens Eye Research Institute have reconstructed an ancient virus that is highly effective at delivering gene therapies to the liver, muscle, and retina.
Cell Aging Slowed by Putting Brakes on Noisy Transcription
Experiments in yeast hint at ways to extend life of some human cells.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!