What do you get when you dissect 10 000 fruit-fly larvae? A team of researchers led by the EMBL- European Bioinformatics Institute (EMBL-EBI) in the UK and the Max Planck Institute of Immunobiology and Epigenetics (MPI) in Freiburg, Germany has discovered a way in which cells can adjust the activity of many different genes at once. Their findings, published online today in Science, overturn commonly held views and reveal an important mechanism behind gender differences.
The female (left) fruit fly, Drosophila melanogaster, is larger than the male (right).
Image credit: EMBL
Asifa Akhtar’s laboratory, previously at EMBL now at MPI, studies precisely how flies regulate an important set of genes. Females have two X chromosomes while males have only one, so the genes on the female X chromosomes somehow need to be kept from producing twice as many proteins as those on the male X chromosome. Male fruit flies get around this by making their X chromosome’s genes work double time: an epigenetic enzyme doubles the output of thousands of different genes. But just how much that doubled output is can vary tremendously from one gene to the next.
“Imagine that you have thousands of half-filled glasses of all different sizes and shapes,” explains Nick Luscombe, who led the work at EMBL-EBI. “Now imagine that you have to fill them all up to the top at the same time. This is an incredibly complex mechanism.”
To see how genes are expressed, scientists try to pinpoint signals that show when a gene increases its output. In most studies of this kind, this output is increased by a factor of between 10 and 100 when a gene is being expressed. In this study, the signal involved is miniscule: an increase of only a factor of two.
Observing such a faint signal is a major challenge. But thanks to the painstaking fly-larvae dissection efforts of graduate student Thomas Conrad, combined with the detailed analytical efforts of Florence Cavalli and Juanma Vaquerizas, the team gathered enough material to measure this output and compare males and females directly.
The scientists found twice as many DNA-transcribing (reading) proteins – known as polymerases – attached to the male X chromosome as to the female version. This means that the difference between males and females is rooted in the beginning of the transcription process, when the polymerase first binds to the DNA. This goes against the commonly held view that the regulation mechanism is kicked off during transcription.
“A factor of two appears minuscule, so it is not easy to measure accurately,” says Akhtar. “We were really doing a bulk analysis of several hundred genes, and that required a lot of careful bioinformatics analysis. Our group would run experiments, Nick’s would analyse the data, and then we would decide on new experiments together to be sure that what we were seeing was real.”
Discovering the machinery that doubles the expression of male X-chromosome genes could well have implications that go far beyond the humble fly. Speaking more technically, Luscombe says: “This is the first direct, clear mechanism that links a histone modification and the activity of a polymerase across thousands of genes”.
Looking into future directions, Akhtar says: “We now need to look more deeply into what makes this kind of mass regulation possible, and how it fits in with other means cells may have to fine-tune their use of genetic information.”
Published online in Science on 19 July 2012. DOI: 10.1126/science.1221428.Policy regarding use
Sonia Furtado Neves | EMBL Research News
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy