In mammalian cells DNA is packaged into chromatin. In our lab we study DNA and chromatin structure to understand gene regulation and genome stability.
Hear a podcast and read a transcript from The Naked Scientists, presented by Nick Gilbert - Twisting DNA.
View a video from The University of Edinburgh about our Chromatin Biology research, presented by Nick Gilbert - Packaging The Genome.
Here’s a photo of us at our 2017 lab retreat to Auchinleck House. We’re back there next week to enjoy a fun week of science - discussing our current research, new techniques and generating new ideas as a team. Hopefully the nice weather holds up for some relaxing walks nearby!
Here, Ryu-suke reviews the role of nuclear RNA’s in organising interphase chromatin structure and contrasts the historical static nuclear matrix model with the emerging dynamic nuclear mesh model.
Our new paper in Molecular Cell. HiP-HoP: A new inter-disciplinary approach to predict complex 3D genome folding.
Inside every cell DNA is wrapped up with proteins to form a structure called chromatin. How chromatin is folded is important for gene regulation and controls how proteins are made in different cell types. Although chromatin folding in cells is complex, chromatin fibres behave much like simple polymers. To investigate the properties important for chromatin folding we setup a collaboration with polymer physicists, to model how chromatin folds at specific genes including those important for human disease. We first collected information about how proteins bound to the DNA at these genes of interest and painted this information onto our computer based 3D polymer simulations. Then, using current knowledge of genome organisation, we added different physical properties to the polymer, such as regions with a more crumpled structure and allowed the computer simulated chromatin polymers to fold-up 100s of different times. We compared the outcome of these simulations to the physical 3D folding of chromatin inside real cells to test how well the model predicted the real 3D structure. The simulations showed us there was striking variability in the shape and folding of chromatin in individual cells, especially at active gene regions and this maybe important for regulating gene expression. We named this method the “highly predictive heteromorphic polymer model” or HiP-HoP model. HiP-HoP now allows us to accurately predict 3D folding using commonly available 2D data and understand some of the fundamental principles that organise DNA inside cells. We are now applying this method to understand how chromatin folding changes in disease, and how this in turn affects the expression of individual genes. Polymer Simulations of Heteromorphic Chromatin Predict the 3D Folding of Complex Genomic Loci
Adams picture of HiP-HoP chromatin made the front cover of Molecular Cell. On the cover: In this issue of Molecular Cell, Buckle et al. (pp.786–797) describe a “highly predictive heteromorphic polymer” (HiP-HoP) model which uses epigenetic and protein binding data to predict the 3D organization of complex gene loci. The image represents a chromatin polymer, simulated as steel beads joined together by flexible springs, within a Waddington landscape. The simulated chromatin fiber has a variable structure with regions of different stiffness generated by additional springs. Two regions of the fiber are shown being brought together to form a loop by bridging transcription factors. Cover design by Adam Buckle.
New paper from Davide in our lab - SMC co-operates with TopoII to efficiently remove knots and links from in vivo chromatin. Read more here.
Adam’s new paper investigating Pax6 cis-regulatory elements in human and mouse was just published at Human Molecular Genetics.
We’re enjoying the second day of the Biophysics of Epigenetics and Chromatin workshop organised by Davide Michieletto from the lab!
Nick’s latest paper has been published in the Journal of Cell Biology:
Issy scooped 2nd place in the University of Edinburgh final of the 3 Minute Thesis Competition, impressing the judges with her ‘Great Genetic Bake Off’ to explain how she is researching the role of chromatin structure in meiotic recombination!
Ryu-Suke’s latest research on the role of SAF-A in the regulation of chromatin structure was published in Cell: SAF-A Regulates Interphase Chromosome Structure through Oligomerization with Chromatin-Associated RNAs.
Congratulations to Issy for winning the IGMM’s Three Minute Thesis competition with her ‘Great Genetic Bake Off’! She will be going on to compete in the University of Edinburgh’s College of Medicine and Veterinary Medicine round. Watch her fantastic talk here:
Hear Nick talk about our latest research at the Chromatin Structure and Function, Gordon Research Conference.
Lora’s new review in Press. Exciting! Boteva, L., Gilbert, N., “Chromatin, nuclear organization and genome stability in mammals “. In Kovalchuk I and Kovalchuk O (Eds), Genome Stability. Cambridge: Elsevier Inc. In Press.
New lab members! Kate and Issy join us to do their PhD’s on chromatin structure and genome stability. Check out their bios.
Nick and Jim visit Diamond Light Source to investigate folding properties of chromatin fibres.
Sam Corless discusses our bioinformatics methods for analysing DNA supercoiling published in Genomics Data.
Interesting paper in Cell from the Lawrence lab. Read our preview Interphase Chromatin LINEd with RNA.
Read our review Supercoiling in DNA and Chromatin in Current Opinions in Genetics & Development.
Our work’s review Divergent RNA transcription: A role in promoter unwinding? was published in Transcription.
Our work Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures was published in Nature Structural & Molecular Biology.