Super-resolution microscopy reveals new epigenetic patterns in chromosomes of egg cells.
This image shows how DNA is packed in a chromosome of a mouse germ cell or oocyte. The left half of the picture is shown at single-molecule resolution, while the right half shows how the same chromosome looks using conventional wide-field microscopy. Taking pictures at this high level of detail has allowed Kirti Prakash in the group of Christoph Cremer at IMB to reveal the detailed structure of these meiotic chromosomes. To achieve this, they looked in particular at the arrangement of different epigenetic marks which are associated with the activation or repression of gene transcription.
Imagine a huge archive full of books on all kinds of different topics. Some are easy to pick up and read, but others are hidden right at the back on unreachable shelves under piles of other books. In order to get to the ones you want, you have to know exactly where to go, and you are more likely to end up reading books that are easy to find.
A similar situation exists in the nucleus of cells. Some genes are tightly packed and others are more easily accessible and readable. Unlike a library, however, the structure of the nucleus and how accessible the genes are constantly changing along the cell cycle. Understanding the way DNA is packed into chromosomes is therefore important for the community to understand how and when different genes are turned on or turned off.
The meiotic chromosome, which is depicted on this image, is found in germ cells (oocytes and spermatocytes). During meiosis, the two chromosomes of the same pair are brought close to each other and parts of the DNA are swapped between them in a process called crossing over. How the structure of the meiotic chromosomes contributes to the process, and how this relates to the transcription of genes remain open questions.
In their recent paper, published in the journal Proceedings of the National Academy of Sciences, they used super-resolution microscopy to look at meiotic chromosomes in unprecedented detail. In particular, they looked at the epigenetic structure of these chromosomes, showing where genes were turned on and off.
They used two markers that allowed them to see more accessible regions of the chromosomes (where genes are turned on) or less accessible regions (where genes are turned off). Interestingly, genes that were turned on were mostly found in interesting loop-like structures that branched out from the chromosome, while the less accessible genes tended to be found in localised regions along the chromosome. Even more interestingly, the different markers were spread along the chromosomes in an unusual alternating pattern (see image).
This is the first time that anyone has investigated the epigenetic structure of meiotic chromosomes at single-molecule resolution. The detailed description of the very distinctive structure of these chromosomes and their epigenetic make-up will help to inform future studies into their function. Moreover, how these patterns, loops, spirals and twists help to avoid chromatin getting tangled or knotted up is still an open question… c’mon, c’mon, c’mon, c’mon work it out!
Prakash K, D Fournier, Redl S, Best G, Borsos M, Parekh S, Ketting RF, Tachibana-Konwalski K, Cremer C and Birk U (2015). Super-resolution imaging reveals structurally distinct periodic patterns of chromatin along the meiotic chromosomes. Proc Natl Acad USA, doi: 10.1073/pnas.1516928112