Researchers at IRB Barcelona discover the molecular mechanism that determines how epigenetic markers influence gene expression
Researchers at the Institute for Research in Biomedicine (IRB Barcelona), Cambridge University and New York University, led by Modesto Orozco, Group Leader at IRB Barcelona, Director of Life Sciences at the Barcelona Supercomputing Center (BSC-CNS) and Professor at the University of Barcelona (UB), have determined the mechanics behind of one of the most common epigenetic modifications: histone-tail acetylation. Acetylation is a means by which a cell can control the expression of its genes.
The study published in the prestigious Journal of the American Chemical Society (JACS) reveals the effect of lysine acetylation in histone tails. "The most relevant acetylation reactions take place in a mysterious part of the nucleosome: the histone tails," explains Modesto Orozco. "Histone tails are loosely structured protein fragments. They are unfolded under normal conditions and when they move, they can touch other nucleosomes, thereby condensing chromatin," he adds. Nucleosomes are structures that make up the fundamental units of chromatin, which is the complex within which DNA is organized in eukaryotic cells.
Using simulation and nuclear magnetic resonance, the researchers found that the histone tails with lysine acetylation acquire a certain structure. "By forming this structure, they become shorter and lose their ability to touch other nucleosomes. As a result, the internucleosomal contact that condenses unmodified chromatin, doesn't happen and this produces DNA molecules that are more accessible to effector proteins and therefore more active," the researcher describes.
This is the first mechanical explanation at the atomic level of an epigenetic effect, one of the most important, that connects an epigenetic modification with a phenotypic effect," assures Orozco. "This leads us to believe that there is a similar explanation for other epigenetic modifications. There may be a very basic mechanism that accounts for the effect that they have on gene structure and expression," he concludes.
Reference article:
Chromatin unfolding by epigenetic modifications explained by dramatic impairment of internucleosome interactions: a multiscale computational study.
Collepardo-Guevara R, Portella G, Vendruscolo M, Frenkel D, Schlick T, Orozco M.
J Am Chem Soc. (2015 Jul 20). PMID: 26192632
Modesto Orozco’s laboratory (IRB Barcelona) has published a study on the source of asymmetry between nucleic acid hybrid (RNA and DNA) in CHEM (Cell Press).
The results are a promising step towards enhancing gene therapies, which are applicable to many diseases.
The Uruguayan newpaper La Diaria has published an article about recent research done by the Molecular Modelling and Bioinformatics Lab at IRB Barcelona. This team has achieved the first stable simulations of DNA crystals, thus allowing the study of the role of each molecular component in the stability and conformation of said crystals. The article includes quotes by Pablo Dans, a postdoctoral researcher at the centre, about the study: "What we want is to see how 3D DNA folding occurs and understand how it correlates with the activity of a specific gene.
Muy Interesante, El Punt AVui, Diario Médico, Laboratory Journal and Federfarma, among other national and international media, have published articles about the research led by Núria López-Bigas, ICREA researcher at IRB Barcelona and that explains the origin of the mysterious periodicity in the genome.
Link to Muy Interesante
