The Welcome Trust Chromatin meeting always draws a ton of interest from the EpiGenie crew, so we were anxious to see what went on at the latest event. We had Max Planck’s Svenja Reinders on site to give us the details, so check out his report below:
Due to a strike on the London underground, actually getting to the venue was an small adventure for several conference attendees that arrived at London airports. Fortunately, everyone made it to the Welcome Trust campus in Hinxton, approximately 30 min outside of Cambridge, without too much hardship.
The Welcome Trust Campus is very modern and green, so it was a pleasure to sit and talk outside during the breaks. The atmosphere was also rather personal, as approximately 150 scientists attended this meeting.
The discovery of TADs and their implications was a hot reoccurring topic as well as unusual histones. Most of the participants of this meeting were also very excited about the CRISPR/Cas9 genetic editing system and they are expecting a lot of new exciting results in the near future.
High-Resolution Histone and Nucleosome Imaging
Kazuhiro Maeshima, National Institute of Genetics (Japan)
Dr. Maeshima held an engaging talk about nucleosome structure which he opened by demonstrating different nucleosome structures with a 3D-model. He first introduced the findings that the text book image of chromatin as an organized string with histone-pearls on it is an artificial-state generated by the low salt content of the buffers used.
In a more native high-salt environment chromosomes are disorganized, leading to less physical constraints and providing a more dynamic structure. Using super-resolution imaging data Maeshima presented live cell imaging movies of labeled histones in the nucleus. His laboratory traced and evaluated the individual histone movements. Even though they saw chaotrophic movement and high fluctuations, they could confirm the existence of topological associated domains (TADs).
Identifying Chromosome Associated Proteins
William Ernshaw, Welcome Trust Center for Cell Biology
The keynote lecture by Dr. Ernshaw was one of the conference highlights. He and his colleagues are interested in identifying centromeric proteins. So by machine learning they are trying to identify “real” chromosome associated proteins. This led them to discover PERP-Proteins which are coating mitotic chromosomes like a “skin” alongside RNA and other unidentified proteins.
His group identified Ki-67 as a master-protein which directs the “skin” to the chromosomes. In Ki-67 knock-out cells he showed by microscopy that the layer around the chromosomes containing over 60 proteins disappears. Cells are also smaller and contain less nuceleoli leading to decreased transcription and unusual positioning of the chromosomes in the cell. In the second part of his lecture his group also showed that the protein condensin is essential for structural integrity of meiotic as well as mitotic chromosomes.
The Role of Chromatin Remodeling Protein ATRX
David Clynes, University of Oxford
The chromatin field is becoming more aware of non-B-DNA structures like G-quadruplex DNA and therefore I would like to point out the talk given by Dr. Clynes from the Richard Gibbons Laboratory at the University of Oxford. Clynes introduced the chromatin remodeling protein ATRX, which targets G-rich tandem repetitive regions on the DNA. He and his colleagues proposed that ATRX helps to incorporate H3.3 into the DNA at sequences that would normally form G-quadruplex structures.
They confirmed that ATRX is also involved in facilitating DNA replication. This was achieved by feeding replicating cells sequentially with nucleotide analogues and consequently analyzing the DNA fibers spread on glass slides, visualized by fluorescence microscopy. By this technique they could trace stalled replication forks and double stranded breaks in ATRX knock out mutants. ATRX interacts with the MNR complex during replication and is involved in alternative telomere lengthening. In knock-outs replication fork stalling is widely observed and subsequent double stranded breaks are a known trigger for homologous recombination.
**EpiGenie gives a huge thank you to Svenja Reinders, M.Sc. for providing this conference coverage. Svenja is currently a PhD student in the Chaperone Research Group at the Max Planck Institute of Psychiatry. **