Ever since people started looking at cells under microscopes in the 19th century it has been known that under certain circumstances chromosomes adopt specific arrangements in the nucleus. A functional interpretation of these arrangements was hindered by the technology available at the time, meaning that chromosomes could only be seen under a few very specific conditions.
It also didn’t help that people didn’t really know what chromosomes were for. During the 20th Century, people discovered that chromosomes contained the genetic material, and further that the chromosomes were linear arrays of genes interspersed with control sequences which were involved in turning the genes on and off. It was clear that the linear relationship between the control sequences and genes was important, but also, at least in some cases, the three dimensional arrangement – how they were arranged in space in the nucleus – played a part. Again, however, the limitations of the available technology prevented a full understanding of this progress. In recent years, technological advances have led to a huge increases in our knowledge of these processes. To mark this, in August,Genome Biologypublished aspecial issueon the three dimensional organization of the nucleus.
Some of the improvements have been in microscopy, where dramatic increases in the achievable resolution mean that chromosome interactions can be probed at a much finer scale. But the main technological advance has been the development of chromosome conformation capture and related techniques, such as the high throughput Hi-C variant. In these experiments, DNA sequences that are close together in space get joined together, and by sequencing it is possible to identify sequences that are widely separated on the chromosome have ended up next to each other. Ferhat Ay and William Noble reviewmethods for analyzing Hi-C data, Takashi Naganoet al.compare results obtained with standard Hi-C and a modified variantshowing how the new protocol improves resolution and reduces artifacts, and Pelin Sahlenet al.present amethod based on Hi-Cwhich enriches for interactions between promoters and enhancers.
Since people first started performing Hi-C, they noticed that some aspects of nuclear organization correlate with specific epigenetic modifications. Hi-C is a laborious and expensive technique, but ChIP-seq to map epigenetic modifications is relatively cheap. In addition, there is a lot of ChIP-seq data from a wide range of cell types already available. It would be therefore useful if it were possible to reconstruct three dimensional organization from epigenetic data. Two methods in the special issue attempt to do just that. Jean-Philippe Fortin and Kasper Hansen’s method canreconstruct ‘A’ and ‘B’ compartments(corresponding to open and closed chromatin) from DNA methylation data, and Jialing Huanget al.show that one canpredict chromatin interaction hubsand topologically associated domain boundaries from histone modification data.
The X chromosome has proved a popular subject in the special issue. In mammals, females have two X chromosomes and males only one, so female cells inactivate one of the two in order to even up the expression levels of genes expressed from the X. Silencing of the inactive X is controlled by the non-coding RNA Xist, and Philip Avner and colleagues discusswhat is known about this processand how Xist affects the structure of the inactive X. Xinxian Denget al.show that theactive and inactive X chromosomes adopt different structures, and Hendrik Markset al.explore thestructure of the various domains of the inactive X, and how the few genes which escape silencing are clustered together.
当然,观察染色体的结构s is interesting, but what is more interesting is what is organizing the structures and what the functional implications of the organization are. A study that addresses the former is Elena Pugachevaet al.‘s study looking at the proteinCTCF and its paralog BORISand how they interact (CTCF is known to be involved in looping parts of the chromosome). Sehrish Rafiqueet al.look at how nuclear organization changes as breast epithelial cells become cancerous.
It is not possible to highlight all of the articles in the special issue individually, so go to theissue page看看我们有什么东西发表,包括塞弗ral excellent reviews. We also have several articles in the pipeline, so keep checking the page over the next few months to see what exciting research we publish.
Indeed. Knowing the structure of chromosome is interesting, and Someday maybe we can see this process just like watching movie, that’s really exciting.