Spatial Arrangement Of Genes Research Articles

Chromosomal origin of replication coordinates logically distinct types of bacterial genetic regulation

For a long time it has been hypothesized that bacterial gene regulation involves an intricate interplay of the transcriptional regulatory network (TRN) and the spatial organization of genes in the chromosome. Here we explore this hypothesis both on a structural and on a functional level. On the structural level, we study the TRN as a spatially embedded network. On the functional level, we analyze gene expression patterns from a network perspective (“digital control”), as well as from the perspective of the spatial organization of the chromosome (“analog control”). Our structural analysis reveals the outstanding relevance of the symmetry axis defined by the origin (Ori) and terminus (Ter) of replication for the network embedding and, thus, suggests the co-evolution of two regulatory infrastructures, namely the transcriptional regulatory network and the spatial arrangement of genes on the chromosome, to optimize the cross-talk between two fundamental biological processes: genomic expression and replication. This observation is confirmed by the functional analysis based on the differential gene expression patterns of more than 4000 pairs of microarray and RNA-Seq datasets for E. coli from the Colombos Database using complex network and machine learning methods. This large-scale analysis supports the notion that two logically distinct types of genetic control are cooperating to regulate gene expression in a complementary manner. Moreover, we find that the position of the gene relative to the Ori is a feature of very high predictive value for gene expression, indicating that the Ori–Ter symmetry axis coordinates the action of distinct genetic control mechanisms.

Multiscale dynamic visualization of signal transduction processes with detailing of target-genes activation in three-dimensional genome structure

Given the complexity of modern biological data it is essentially crucial to accord a consistent expounding. Interpreting such data into complex networks and visualizing them can reveal understanding of various processes in a cell. A consequence mapping of signal transduction processes to the spatial genome structure can benefit new insights in interaction detection in the spatial arrangement of genes. We present an approach for multiscale dynamic visualization of signal transduction processes with detailing of target-genes activation in spatial genome structure. The usage of this approach is demonstrated for the WNT signaling pathway in a human cell. We conclude with suggesting future research questions to improve our approach by considering new available data.

Effects of Fluctuation of Chromosome Conformation and Spatial Arrangement of Genes on the Pattern of Gene Expression

Recently, conformation of all chromosomes in the interphase nucleus of budding yeast has been inferred from the Chromosome Conformation Capture-on-Chip (4C) data (Duan et al., Nature (2010)). However, it has not yet been ascertained how the conformational fluctuation around their mean structures affects the regulation of gene expression. To clarify this issue, we developed a dynamical structural model of interphase chromosomes in budding yeast (Tokuda et al., Biophys. J. (2012)). In the present paper, the effects of the conformational fluctuation and the arrangement of genes on the pattern of gene expression are discussed by using this coarse-grained chromosome model. In particular, the observed difference in the pattern of gene expression between the yku70 esc1 mutant which abrogates telomere anchoring and the wild-type strain (Taddei et al., Genome Res. (2009)) is studied. In the data of Taddei et al., 32 genes are expressed at higher levels and 28 genes are expressed at lower levels in the yku70 esc1 mutant than in the wild-type strain. We examine the reason of this misregulation by comparing the fluctuation of the chromosome conformation and spatial arrangement of genes in the case that telomeres are not anchored to the nuclear periphery with that in the anchored case.

Tissue Distribution and Gender-Divergent Expression of 78 Cytochrome P450 mRNAs in Mice

Cytochrome P450 (Cyp) enzymes from the first four families (Cyp1-4) play a major role in metabolizing xenobiotics, affecting drug pharmacokinetics and chemical-induced toxicity. Due to cloning of the mouse genome, many novel Cyp isoforms have been identified, but their tissue distribution of expression is unknown. This study compared the tissue distribution of all 78 Cyps from the Cyp1-4 families in C57BL/6 mice providing not only an indication of which tissues novel Cyps may have their greatest importance but also a cohesive comparison of the tissue distribution of all Cyp1-4 isoforms. Transcripts of the 78 Cyps were quantified by multiplex suspension arrays and quantitative real-time PCR in 14 tissues. Hierarchical clustering indicated that in male mice, 52% of the Cyp species were expressed highest in liver, 10% in kidney, 10% in duodenum/jejunum, 10% in testes, 5% in lung, and < 4% in colon, brain, heart, and stomach. Female mice had a similar pattern of Cyp messenger RNA expression; however, compared with males, females had 7% more Cyps that were liver predominant, 2% more Cyps that were stomach predominant, but 1% less Cyps that were kidney and lung predominant. Differences in gender expression were observed in 29 of the Cyps, with 24 being higher in females than males. Additionally, the data suggest a correlation between the spatial arrangement of genes within a gene cluster and their organ-predominant expression, indicating a common regulatory mechanism may be present within these clusters. In conclusion, this study provides novel data on the tissue distribution and gender-divergent expression of 78 functional mouse Cyp isoforms.

Spatial arrangement of genes, centromeres and chromosomes in human blood cell nuclei and its changes during the cell cycle, differentiation and after irradiation.

Higher-order compartments of nuclear chromatin have been defined according to the replication timing, transcriptional activity, and information content (Ferreira et al. 1997, Sadoni et al. 1999). The results presented in this work contribute to this model of nuclear organization. Using different human blood cells, nuclear positioning of genes, centromeres, and whole chromosomes was investigated. Genes are located mostly in the interior of cell nuclei; centromeres are located near the nuclear periphery in agreement with the definition of the higher-order compartments. Genetic loci are found in specific subregions of cell nuclei which form distinct layers at defined centre-of-nucleus to locus distances. Inside these layers, the genetic loci are distributed randomly. Some chromosomes are polarized with genes located in the inner parts of the nucleus and centromere located on the nuclear periphery; polar organization was not found for some other chromosomes. The internal structure of the higher-order compartments as well as the polar and non-polar organization of chromosomes are basically conserved in different cell types and at various stages of the cell cycle. Some features of the nuclear structure are conserved even in differentiated cells and during cellular repair after irradiation, although shifted positioning of genetic loci was systematically observed during these processes.

Nuclear domains involved in RNA synthesis, RNA processing, and replication.

Two main principles of nuclear organization have been outlined on the basis of contributions by many research groups in recent years. The first principle is that interphase chromosomes occupy discrete territories in the nucleus, with no intermingling of the DNA from different chromosomes. Within a chromosome territory the DNA is organized in chromatin fibers at several levels of folding, that meander through the territory. Transcription and replication take place at the surface of these higher order chromatin fibers, probably on locally unfolded DNA templates. The second principle is that different types of nuclear domains are associated with several specific gene loci. This holds for clusters of interchromatin granules, coiled bodies, RNA 3'-cleavage factor-containing nuclear bodies (cleavage bodies) and probably PML-containing nuclear bodies. These domains may play an important role in the spatial arrangement of genes in the interphase nucleus. Despite these new insights, our knowledge of the function of many nuclear compartments and the molecular interactions responsible for the dynamic organization of a compartmentalized nucleus is still in its infancy.

Spatial arrangement of genes and chromosomes in plants comments on cell geneology and tissue specificity

In this contribution we discuss the spatial arrangement of plant chromosomes and genes during interphase and mitosis. Apart from certain regularities with respect of their localization (which might have a functional significance) we stress the point that spatial position is also determined by the geneology of the cell.