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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>