Chromosomal organization at the level of gene complexes

Metazoan genomes primarily consist of non-coding DNA in comparison to coding regions. Non-coding fraction of the genome contains cis-regulatory elements, which ensure that the genetic code is read properly at the right time and space during development. Regulatory elements and their target genes define functional landscapes within the genome, and some developmentally important genes evolve by keeping the genes involved in specification of common organs/tissues in clusters and are termed gene complex. The clustering of genes involved in a common function may help in robust spatio-temporal gene expression. Gene complexes are often found to be evolutionarily conserved, and the classic example is the hox complex. The evolutionary constraints seen among gene complexes provide an ideal model system to understand cis and trans-regulation of gene function. This review will discuss the various characteristics of gene regulatory modules found within gene complexes and how they can be characterized

Genome-Wide Tissue-Specific Occupancy of the Hox Protein Ultrabithorax and Hox Cofactor Homothorax in Drosophila

The Hox genes are responsible for generating morphological diversity along the anterior-posterior axis during animal development. The Drosophila Hox gene Ultrabithorax (Ubx), for example, is required for specifying the identity of the third thoracic (T3) segment of the adult, which includes the dorsal haltere, an appendage required for flight, and the ventral T3 leg. Ubx mutants show homeotic transformations of the T3 leg towards the identity of the T2 leg and the haltere towards the wing. All Hox genes, including Ubx, encode homeodomain containing transcription factors, raising the question of what target genes Ubx regulates to generate these adult structures. To address this question, we carried out whole genome ChIP-chip studies to identify all of the Ubx bound regions in the haltere and T3 leg imaginal discs, which are the precursors to these adult structures. In addition, we used ChIP-chip to identify the sites bound by the Hox cofactor, Homothorax (Hth). In contrast to previous ChIP-chip studies carried out in Drosophila embryos, these binding studies reveal that there is a remarkable amount of tissue- and transcription factor-specific binding. Analyses of the putative target genes bound and regulated by these factors suggest that Ubx regulates many downstream transcription factors and developmental pathways in the haltere and T3 leg. Finally, we discovered additional DNA sequence motifs that in some cases are specific for individual data sets, arguing that Ubx and/or Hth work together with many regionally expressed transcription factors to execute their functions. Together, these data provide the first whole-genome analysis of the binding sites and target genes regulated by Ubx to specify the morphologies of the adult T3 segment of the fly

Identification of Genes That Promote or Antagonize Somatic Homolog Pairing Using a High-Throughput FISH–Based Screen

The pairing of homologous chromosomes is a fundamental feature of the meiotic cell. In addition, a number of species exhibit homolog pairing in nonmeiotic, somatic cells as well, with evidence for its impact on both gene regulation and double-strand break (DSB) repair. An extreme example of somatic pairing can be observed in Drosophila melanogaster, where homologous chromosomes remain aligned throughout most of development. However, our understanding of the mechanism of somatic homolog pairing remains unclear, as only a few genes have been implicated in this process. In this study, we introduce a novel high-throughput fluorescent in situ hybridization (FISH) technology that enabled us to conduct a genome-wide RNAi screen for factors involved in the robust somatic pairing observed in Drosophila. We identified both candidate “pairing promoting genes” and candidate “anti-pairing genes,” providing evidence that pairing is a dynamic process that can be both enhanced and antagonized. Many of the genes found to be important for promoting pairing are highly enriched for functions associated with mitotic cell division, suggesting a genetic framework for a long-standing link between chromosome dynamics during mitosis and nuclear organization during interphase. In contrast, several of the candidate anti-pairing genes have known interphase functions associated with S-phase progression, DNA replication, and chromatin compaction, including several components of the condensin II complex. In combination with a variety of secondary assays, these results provide insights into the mechanism and dynamics of somatic pairing

Characteristics of innovation policy mixes in multi-level government system: the case of the Baltic Sea Region countries

Elektroniskā versija nesatur pielikumusPromocijas darbā pētīts, kā notiek inovācijas rīcībpolitikas paralēla plānošana un ieviešana dažādos pārvaldes līmeņos – vietējā, nacionālā un pārnacionālā. Analizētas divas gadījumu grupas – Baltijas valstis un Somija, Zviedrija un Dānija – kas atšķiras pēc inovācijas rīcībpolitikas īstenošanā aktīvi iesaistīto pārvaldes līmeņu skaita. Darba teorētiskais ietvars ir daudzlīmeņu pārvaldības un rīcībpolitiku kombināciju koncepti, kas izmantoti kvalitatīvo datu analīzes kategoriju izstrādei. Gadījumi analizēti un salīdzināti, izmantojot politikas plānošanas dokumentus un veicot padziļinātās intervijas ar rīcībpolitikas veidotājiem katrā pārvaldes līmenī. Hipotēze, kurā tika pieņemts, ka daudzlīmeņu inovācijas rīcībpolitikas kombinācijas raksturo nesaskaņotība, netika pierādīta, taču starp pārvaldes līmeņiem nevar novērot arī pozitīvu sinerģiju.Dissertation explores how innovation policy is planned and implemented at different levels of government - local, national and transnational. Two groups of cases are analysed - the Baltic States and Denmark, Sweden and Finland. The groups of cases differ according to the number of government levels involved in the innovation policy making. The theoretical frameworks of the thesis are the concepts of policy mix and multi-level governance. Both are used to develop the categories for qualitative data analysis. The cases are analysed and compared using the policy planning documents and conducting in-depth interviews with policy makers at each level of government. The hypothesis, which assumed that multi-level innovation policy mixes are incoherent, was not proved, however, interaction between government levels was not identified either