Russian Science Foundation: Biologists figure out how lampbrush chromosomes ensure the proper development of chicken embryos
A group of researchers from St Petersburg are studying gene expression in lampbrush chromosomes — these are a special form of chromosomes found in the oocytes of all vertebrate species, except mammals. The research findings indicate extensive transcription of a number of genes on the lampbrush chromosomal loop structures, including genes involved in early embryo development. In future, this discovery may enable us to induce epigenetic modifications of beneficial genes in domestic chickens during oogenesis.
A genome provides all the information the organism requires to function. Inevitably, scientists seek to understand how genomes — that is, the sets of genetic information — of various creatures are arranged. For this purpose, it is important to determine not only the sequence of nucleotides letters in the genome, but also the localisation and functions of specific genes. Genes can be active, with genetic information being copied from them and certain proteins being synthesised, or they can be inactive, in which case they are dormant or silent. Active genes, positioned side by side on a chromosome, — a twisted strand of DNA surrounded by proteins — are often arranged into groups that outwardly resemble dense balls or beads on a string.
The findings of the research, supported by a grant from the Russian Science Foundation (RSF), are published in the journal Chromosoma.
During oocyte development, the chromosomes change their structure, with their shape varying significantly in different animals. For example, the chromosomes in the growing oocytes of avians, amphibians, and some other vertebrates resemble bristled brushes for cleaning oil lamps. Hence, they are called lampbrush chromosomes. They display readily distinguishable regions of transcriptional activity — lateral loops that extend as symmetrical pairs from regions along the chromosome axis. Thus, lampbrush chromosomes unfold and become so gigantic that the details of their structure can be examined under a light microscope.
The researchers from St Petersburg University have studied the changes in gene activity on chromosomes when they transition into lampbrush chromosomes. To distinguish between these segments of DNA, the researchers labelled them with three-coloured fluorescent molecular tags. Thus, if several fluorescent tags attached to the DNA segments begin to glow side by side, it can be inferred that these DNA segments are positioned adjacent to one another. The object of the research is maturing chicken oocytes.
During mitosis (i.e. somatic cell division), groups of active genes converge in the space within the nucleus, forming separate chromatin domains. During cell division, active genes are assembled into topologically associating domains (TADs), which, apparently, enables them to interact with each other. The researchers have investigated whether somatic TADs are preserved when somatic chromosomes form lampbrush chromosomes during meiosis. Meiosis is a special type of cell division that reduces the number of chromosomes in the parent cell by half so that later, when the sex cells merge, a complete set of chromosomes is produced. The research findings have confirmed the presence of lampbrush chromatin domains in separate dense balls on a string. However, the lampbrush chromatin domains do not overlap with TADs observed in somatic cells.
In future, the obtained results may enable us to induce epigenetic modifications of target genes in domestic chicken during oogenesis; for example, genes responsible for quantitative traits, such as egg production.
Alla Krasikova, Associate Professor in the Department of Cytology and Histology, the Faculty of Biology at St Petersburg University
In addition, the researchers have mapped the transcriptionally active genes in the growing chicken oocytes — these genes are responsible for the proper oocyte and embryo development. On the lampbrush loops, there are more active genes compared to other areas. From some of these active genes, for instance, from the CNOT7 gene, the so-called maternal RNA genes are copied. Maternal mRNAs are stored in the oocyte and used for protein synthesis in the embryo. Also, on the lampbrush loops, regions were found where non-coding RNA genes are formed — non-coding ncRNAs are involved in gene regulation. These findings confirm that functionally significant transcription takes place on lampbrush chromosomes — RNA synthesis on a DNA template. This refutes the assumption that the nascent RNA transcripts generated on lampbrush chromosomes are not product of specific genes and they do not code for active biomolecules.
‘The study of chromatin folding and gene expression of maturing oocytes is basic research. It enables deeper understanding of genome architecture and function. Our findings are consistent with the data obtained earlier on amphibian lampbrush chromosomes. In the short run, we plan to describe the entire spectrum of RNAs synthesised on lampbrush loops in avians. Perhaps, in future, the obtained results will enable us to induce epigenetic modifications of target genes in domestic chicken during oogenesis, for example, of genes responsible for quantitative traits, such as egg production. Such research and experiments are of particular significance due to the fact that avians are widely used as model organisms in embryology,’ stressed Alla Krasikova, Principal Investigator of the project supported by a grant from the Russian Science Foundation, Candidate of Biology, Associate Professor in the Department of Cytology and Histology, the Faculty of Biology at St Petersburg University.