Indicator: The appearance of chromosomes in sex cells linked to gene activity

The authors compared large regions of chromosomes in sex and somatic − that is, all other − chicken cells, and found similarities in the spatial arrangement of their genomic DNA with different densities of protein-coding genes. The information on the relationship between chromosome appearance and genetic activity sheds light on the fundamental mechanisms of how genes work in the cell nucleus.

The findings of the research supported by a grant from the Russian Science Foundation are published in Epigenetics & Chromatin.

Vertebrate genomes, including human genomes, can be divided into two large parts depending on how many protein-coding genes they contain. These are conventionally called compartments A and B. Compartment A corresponds to the regions of chromosomes where transcription, i.e. reading of information about RNA from DNA, is active. The second part, compartment B, on the contrary, corresponds to the regions that contain almost no protein-coding genes and represents the so-called repressive regions, which are rich in repeats and other regulatory elements of DNA. The transcriptional activity of genes is closely linked to the spatial arrangement of genetic information, or genome architecture. The fact is that special proteins − transcription factors − help to read information from DNA. In order for them to join DNA, this molecule, which is normally tightly twisted like a tangle of threads, must ‘unravel’ and straighten. The 3D genome architecture and the transcriptional mechanisms together maintain a long-term state of active or repressive chromatin status at each specific DNA domain. Disruption of DNA architecture can lead to the development of various diseases, including cancer. Therefore, the more we know about the molecular mechanisms of changes in the 3D structure of DNA, the better we will be able to understand how to treat related diseases.

The scientists from St Petersburg University (St Petersburg) have compared the structure of DNA molecule stacking and genetic activity in somatic, i.e. ordinary body cells, and in oocytes (female germ cells) of chickens. When a cell becomes specialised during the development of the organism, for example, when it becomes an epithelial, nerve, or sex cell, the architecture of the genome also changes, and this affects gene activity. Comparison of sex cells and somatic cells helps to better understand the principles of genetic information packaging.

In avian oocytes, there is intense synthesis of the RNA needed for the production of proteins for the future embryo, which therefore indicates active transcription. This, in turn, affects the appearance of chromosomes: they become tens of times larger than somatic cell chromosomes, can reach one millimetre in length, and are clearly visible even in an ordinary microscope. Additionally, they have a characteristic pattern that resembles a petroleum lamp brush, which is why they are called lampbrush chromosomes. The axis of such a ‘brush’ consists of a chain of chromomeres − clusters of densely packed chromatin arranged in a row. RNA synthesis is virtually absent in these regions, because there are almost no genes that contain information about protein structure. Loops, each consisting of a DNA strand with very intense transcription, branch off from this ‘inactive’ axis.

In somatic cells, it is extremely difficult to analyse both transcriptional activity and genome architecture simultaneously. Their small size also complicates the analysis, whereas giant chromosomes in oocytes may help to reveal universal mechanisms of chromatin separation into active and inactive parts.

Alla Krasikova, Principal Investigator, Associate Professor in the Department of Cytology and Histology of St Petersburg University, Head of the Laboratory of Structure and Dynamics of Cell Nucleus, Candidate of Biology

The authors isolated genetic material from chicken connective tissue cells. Then, they compared the resulting DNA sequences with chromosome stacking in oocytes, paying attention to which genes are in active and repressive domains. To distinguish these domains, the scientists labelled them with different glowing DNA probes − short sequences of nucleotides, which were attached to precisely defined parts of the chromosome. As a result, the researchers found out from the difference in luminescence that the boundaries between active and repressive regions do not correspond to the boundaries of chromomeres. Instead of one large inactive region, the scientists observed several small repressive domains on the DNA strand.

Thus, the scientists found that in both sex cells and somatic cells, regions of active chromatin correspond to chromosome segments consisting of ‘clusters’ of small loose chromomeres and long lateral loops. Areas with large ‘clusters’ and short loops correspond to tightly twisted repressive regions with low gene density and inactive transcription.

‘In future, we plan to study the mechanisms of formation of individual chromomeres. It is also interesting to study the very mechanism of hypertranscription in the oocyte and the effect of ultrafast RNA synthesis on lampbrush chromosomes on gene activity,’ said Alla Krasikova.