Proceedings of The Sophia - Antipolis Spring School on M odelling C omplex B iological S ystems in the C ontext of G enomics

The Unified Matrix Hypothesis (UMH) proposed that genomes may be organised in space, and genomic domains be transcribed in specific sectors of the nucleus [1]. The UMH generalised for normal types of interphase cells, the pattern of Ectopic Pairing observed in drosophila salivary gland cells. The recent publication of the 3D structure of the yeast genome [2] is clear confirmation in lower eukaryotes of the UMH concept. Genomic domains of higher eukaryots are visible in polytene chromosomes of sciaridae and drosophila (C-value up to 10 000) as bands, representing units of transcription and meiotic recombination, which are held in 3D positions by ectopic cables linking distant interbands, within and in between chromosomes, as well as the nucleolus; in this type of cell, this pattern is genetically determined [1]. DNA in normal cells is flexible and able to link directly distant sites within and between chromosomes as obvious in yeast [2]. Of conceptual importance within the UMH concept is that DNA length per se represents genetic information, independent of sequence, as a basis of nuclear architecture and cellular morphogenesis. Specific types of cells have changing patterns of heteroand euchromatin; the phenomenon of “quantal mitosis” [1] shows that differentiation can be stopped by agents blocking chromatin remodelling. 3D DNA organisation determines chromosome territories, which are relatively stable including heterochromatin. Euchromatin, however, may participate in additional more flexible DNA interactions, which are conditional for individual gene expression, as shown in case of association of the distant TH2 cytokine and IFN-γ loci [3]; such “3D gene regulation” recalls the pattern observed in yeast [2]. Within the Genon concept of regulation [4, 5], 3D genome organisation may represent the highest-level program of gene expression encoded in the entire genome. Downstream, the expression of genomic domains and individual genes is implemented by transcription, differential splicing of pre-mRNA, mRNA transport as well as repression or activation, which are controlled in cis by the sequential expression of genetic programs termed protogenon for the domains, pre-genon for pre-mRNA, and genon for mRNA. This cis information MODELLING COMPLEX BIOLOGICAL SYSTEMS 13