Genetic Choreography of the Developing Human Embryo
“the discovery of a major new programme of non-coding transcription adds a fresh layer of detail on the spatiotemporal regulation of the human genome.”
the identification of a role for non-protein-encoding RNAs in sculpting the organs of the embryo is on a par with that of the finding that genes are in pieces – the introns snipped out, leaving only the exons to encode protein
The discovery of introns instantly dispelled the long-held view of the gene as a single, sleek, DNA code for an RNA molecule.
Like introns, LINC RNAs were also once not well understood because they do not encode protein. The wonder of genetics is that we often think that we know close to all there is to know, only to discover yet another hidden language of life.
The Choreography of Fertilization
At fertilization, a continuum is established between the final phases of oogenesis and the formation of a new individual. In mammals, the two processes are overlapped. The fertilizing spermatozoon represents the paternal contribution to zygote constitution and at the same time the trigger for the completion of meiosis. Oocytes can mimic fertilization, being able to recapitulate autonomously many of the events of early embryonic development. However, without the sperm contribution development to term cannot occur. The sperm, in fact, carries not only the paternal chromosomes, but also cytoskeletal elements and biochemical cues that are essential to complement and regulate the oocyte cellular legacy. Therefore, oocyte-sperm fusion creates a unique cellular machinery whose regulation in time and space influences the long term destiny of the ensuing embryo.
Fertilization precisely choreographs parental genomes by using gamete-derived cellular factors and activating genome regulatory programs. However, the mechanism remains elusive owing to the technical difficulties of preparing large numbers of high-quality preimplantation cells. Here, we collected >14 × 104 high-quality mouse metaphase II oocytes and used these to establish detailed transcriptional profiles for four early embryo stages and parthenogenetic development. By combining these profiles with other public resources, we found evidence that gene silencing appeared to be mediated in part by noncoding RNAs and that this was a prerequisite for post-fertilization development. Notably, we identified 817 genes that were differentially expressed in embryos after fertilization compared with parthenotes. The regulation of these genes was distinctly different from those expressed in parthenotes, suggesting functional specialization of particular transcription factors prior to first cell cleavage. We identified five transcription factors that were potentially necessary for developmental progression: Foxd1, Nkx2-5, Sox18, Myod1, and Runx1. Our very large-scale whole-transcriptome profile of early mouse embryos yielded a novel and valuable resource for studies in developmental biology and stem cell research. The database is available at http://dbtmee.hgc.jp.
Rif1 choreographs DNA replication timing
Eukaryotic cells duplicate their genome in a pre‐determined order that appears to reflect a fundamental property of chromatin. Each chromosomal region replicates at a consistent, developmental‐ and tissue‐specific time during the S phase of the cell cycle, and regions that replicate at the same time form distinct patterns in three‐dimensional nuclear space. Although orderly progression of DNA replication is important for insuring stable genetic and epigenetic inheritance, the mechanisms underlying replication patterns have yet to be elucidated.
New work identifies Rif1 as a global determinant of the timing program that controls orderly progression of mammalian DNA replication to ensure stable genetic and epigenetic inheritance.
Common Design 