Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

GenoMyc binding

30.04.2003


Two papers in the May 1 issue of Genes & Development reveal unexpectedly widespread genomic binding by the Myc protein – prompting scientists to consider that this highly studied human oncogene may still have a few secrets to reveal.



Independent research groups led by Drs. Robert Eisenman (Fred Hutchinson Cancer Center) and Bruno Amati (European Institute of Oncology) report on the first genome-wide analyses of in vivo Myc targets in the Drosophila and human genomes, respectively. As the myc gene is mutated in approximately one-third of all human cancers, the identification of the full range of genes that interact with Myc under normal conditions will be important to understanding how abnormal myc expression can lead to cancer.

The myc gene encodes a transcription factor (Myc) that, together with a partner protein (Max), binds to specific DNA sequences to regulate gene expression. myc is classified as an oncogene because genetic mutations that result in over-expression of Myc protein promote unregulated cell proliferation and cancer. While Myc has an established role in directing cell growth, proliferation, differentiation, and death, the precise molecular pathways of Myc action are still largely unknown.


"A major problem in understanding how Myc exerts its profound effects on cellular functions has been the determination of the nature and number of its binding sites on DNA," states Dr. Eisenman. Previous attempts to identify Myc-regulated genes have provided incomplete pictures of Myc targets, complicated by such issues as direct versus indirect interactions and physiological relevance.

These two papers represent a significant advance in the effort to identify DNA sequences that bind Myc. Using completely different experimental approaches and biological systems, both research teams arrived at a similar result: Myc binds to ~10% of all genes.

Dr. Eisenman and colleagues used Drosophila to study where Myc (and its associated proteins, Max and Mnt) binds to in the fly genome. The researchers employed a so-called "DamID approach" to tag Myc-binding sites. By expressing a fusion protein of the bacterial Dam methylase enzyme with Myc in fly cells, Dr. Eisenman and colleagues were able to mark each region of Myc binding with methyl groups. The presence of these "methylation markers" enabled the researchers to distinguish regions of direct Myc-binding from the rest of the genome, isolate the sequences of interest, and then use microarray analysis to identify the encoded genes.

In contrast, Dr. Amati’s group used human cells to identify Myc target genes. The researchers focused on those genes that bind Myc through the consensus "E-box" DNA sequence (CACGTG). Dr. Amati and colleagues used bioinformatics tools to scan the human genome and identify genes containing one or more E-boxes in the proximity of their promoter (the portion of the gene where transcription begins). Of the 1630 gene loci identified, approximately 700 underwent further biochemical characterization to determine which E-box-containing genes bind Myc in vivo. As in flies, the results were surprising.

As Dr. Amati explains, "In addition to identifying 257 genes that are bound by Myc in the human genome, our data also reveals that Myc must bind at least one tenth of all cellular genes or, in other words, several thousand genes. This unexpected degree of complexity is a fundamental feature that is conserved between humans and flies."

Taken together, these two studies provide the most comprehensive enumeration of direct, in vivo Myc targets. The conclusion that Myc binds a large portion of both the fly and human genome dramatically alters previous views of Myc’s activity and the complexity of its biological interactions. Rather than consider a limited number of genes to be targets of Myc, it is now apparent that Myc exerts an extremely widespread influence over the vertebrate genome.

Heather Cosel | EurekAlert!
Further information:
http://www.cshl.org/

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

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,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

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...

Im Focus: Circular RNA linked to brain function

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...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

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...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>