Once more, the longstanding biennial EMBL meeting on Chromatin and Epigenetics in Heidelberg (Germany) draw together an exciting crowd of presenters and listeners, discussing latest finding in the field.
The talks covered (but were not restricted to) topics such as the inheritance of epigenetic marks during cell replication and development, chromatin dynamics and signaling (e.g. transcription factor binding dynamics, targeting and loading of histones), the regulation of imprinting and new upcoming technologies in the field.
As a highlight, the longstanding question of how histone marks are re-established after replication was addressed with several excellent talks and posters showing that different histone marks have different kinetics. Acetylation marks are very quickly established, while re-establishment of trimethylation, on the other hand, is very slow.
3D chromatin structures were the hottest topic of the meeting with chromatin–chromatin interactions (promoter–promoter or promoter–enhancer) being discussed by many. The Furlong lab (among others) showed that chromatin interactions seem to prime transcription during development but are not necessarily instructive. Other talks demonstrated that structural changes in topologically associating domains (TADs) alter promoter–enhancer interaction and subsequently gene expression. Especially hot in the field is modeling of chromatin 3D structures and new technology development.
With such a high caliber of talks it was difficult to select just a few to cover, but here are my top picks from the meeting:
Genome regulation during embryonic development
Eileen Furlong, EMBL Heidelberg, Germany
Using Bits-4c-seq (developed by the group of Wooster de Laat) the Furlong Lab set out to investigate chromatin interactions during development, both before and during cell fate decision. Surprisingly, they found that only ~6% of interactions were dynamic and most of those reflecting enhancer to promoter proximity (30%) were not actually correlated with changes in gene expression. Further investigation showed that most of these promoters had poised marks and were associated with Pol2 pausing.
Novel, ligation-free method for identifying chromatin interactions genome-wide
Ana Pombo, Max-Delbrück-Centre for Molecular Medicine, Germany
Wouldn’t it be great to look at both chromatin–chromatin contacts and their position within the nucleus at the same time? How about not only looking at pairwise interaction but multiple interactions? Over the last 10 years Ana Pombo’s group has developed a technique utilizing micro cryosections of the nucleus of single cells. They found that regions with single contacts are located closer to the periphery whereas those with multiple contacts were located further away. Additionally, multiple contacts were typically between active regions and contained super-enhancers.
Toward physical principles of chromatin (re)organization
Leonid Mirny, Massachusetts Institute of Technology, USA
Leonid Mirny and his group have used Hi-C data to propose a biophysical model of loop extrusion to explain 3D chromatin folding. The loops are predicted to form consecutively and cover a significant amount of the genome (50–70% in metaphase chromosomes). The extrusions are (possibly) performed by Structural Maintenance of Chromosomes proteins (SMC) complexes, which slide freely within TADs but are stopped at the boundaries. It impresses by its simplicity – only two major parameters are required: the average loop length (80–120kb) and ‘processivity’. The model can reproduce features of TAD organization as well as the segregation of sister chromatids during mitosis.
Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions
Darío G. Lupiáñez, MPI for Molecular Genetics, Germany
Not many studies have been able to explain the functionality of TAD organization, so this study of the extended WNT6/IHH/EPHA4/PAX3 locus required for limb development might well be considered a pioneer. Using a mouse model created with adapted CRISPR technology, Darío shows that mutations of the locus result in structural changes, which create ectopic interactions between promoters and non-coding DNA of adjacent TADs. A cluster of limb enhancers normally associated with Epa4 is misplaced relative to TAD boundaries, causing it to interact with Wnt6 and driving ectopic limb expression of Ihh or Pax.
Systematic characterization of the KRAB zinc finger proteins family using high-resolution ChIP-Seq
Michael Imbeault, EPFL, Switzerland
KRAB proteins make up about half of all zinc finger proteins, which in turn make up about half of all known transcription factors. Using high resolution ChIP-exo Michael presented a first large-scale characterization of these proteins revealing significant species specificity and preferences for LTR binding. Interestingly the binding of LTR promoter elements by KRAB proteins appears (for certain elements) to correlate with the evolutionary age of the repeat, being stronger for older and weaker for newer elements.
Common threads: epigenetics, metabolism and the clock
Paolo Sassone-Corsi University of California Irvine, USA
Environmental influences have been long associated with epigenetic mechanisms. Paolo Sassone-Corsi presented how the deacetylaes SIRT1 and SIRT, as well as MLL1 in its role as a H3K4 methyltransferase are instructive for our circadian clock. The key component is circulating NAD+, which through its strong connection to energy metabolism demonstrates not only the importance of light influence but also feeding behavior on to the circadian clock.
Ever wondered why airlines serve food at time fixed to the local time at destination? Now you know!
This summary just shows a selection of some of the many exquisite talks. The conference contained a wonderful selection of talks and poster sessions, which were matched by flawless organization and rounded up by an impressive banquet/party on Saturday night.
** Thanks to Angelika Merkel at the Genome Sequencing Center (CNAG) in Barcelona, Spain
for providing this coverage.