Biopolym. Cell. 2019; 35(3):179-180.
Chronicle and Information
From 3D-genome organisation to cellular and supra-cellular morphogenesis
- Institut J. Monod, CNRS and Univ. Paris Diderot
The molecular 3D-model of the "Unified Matrix Hypothesis" (UMH) proposed that the eukaryotic DNA may be organised in a 3D-network and genomic domains, to be transcribed in specific sectors of the nucleus defining "chromosome territories"(1). It generalised by analogy for normal cells the pattern of Ectopic Pairing observed since 1948 in drosophila salivary glands, that links the 4 polytene chromosomes and the nucleolus into a 3D-genomic network. In normal cells where DNA is flexible, an analogous system might operate able to link directly distant sites within and between chromosomes. This putative model at the basis of nuclear architecture and morphogenesis was confirmed by the publication of the 3D structure of the yeast genome (2) and more recently extended to eukaryotic cells in general (2). The original model of the UMH also proposed a logical link between cellular and supra-cellular morphogenesis. - The 3D-DNA chromatin network organises the nuclear architecture which can be modified back and forth by conversion of hetero- and euchromatin, or by transposition of mobile DNA elements as SINES and LINES or other "jumping genes". In undifferentiated stem cells and de-differentiated cells, having lost their cytoplasm by "shedding", the nucleus occupies most of the cellular volume. In differentiation, it is reduced by retraction of its membrane from the periphery to the center, ending up fully picnotic in terminal differentiation of, e.g. red cells,. In this process, nuclear space becomes cytoplasm leaving behind, possibly, some of its organisation. In the cytoplasm localised synthesis of specific proteins is based on prior 3D-sorting of mRNA; the various types of cytoskeleton are instrumental in this process, in particular the IF and the tubulin network. The latter is organised from the centrosome positioned at the nuclear membrane. - Prior to cell division the centrosomes divide and move to opposite poles of the cell from where the spindle is formed in mitosis; this determines the direction of cellular division in space. However, prior to daughter cell formation the spindle may change its position within the cellular space. Programs of spindle (re-)orientation define the direction of subsequent cell divisions; combined with allowed numbers of divisions this fixes primary morphogenesis, prior to cell-cell interaction and selective apoptosis. Spindle re-orientation happens at critical steps of differentiation and morphogenesis and is based on the internal topological organisation of the mitotic cell. Thus, 3D organisation of the human genome, transcripts and gene expression may link DNA polymorphism and supra-cellular morphogenesis in individuals, as a paradigm of, e.g., definition of facial patterns obviously linked to genetics.