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The importance of higher order nuclear structure and compartmentalization for the control of the cell life is now indisputable. The genome of higher eukaryotes is organized into definite chromosome territories, and the three-dimensional organization of these territories may be intently related to genomic function, global regulation of gene expression, and even formation of exchange aberrations. In this review, we discuss our current understanding of the chromosome territories phenomenon and briefly describe how genes relocation in three-dimensional arrangement of the genome may influence their functioning. We explain how the intermingling of the edges of chromosome territories allows the formation of rare long-range interchromosomal interactions. Moreover, we illustrate recent discoveries describing the mechanisms of physical proximity-based chromosome translocations and its clinical consequence for fusion genes formation and tumor development. Finally, we characterize the inner structure of the intermingled chromosomes briefly, and explain how chromosome intermingling affects gene expression regulation.

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The eukaryotic genome, constituting several billion base pairs, must be contracted to fit within the volume of a nucleus where the diameter is on the scale of µm. The 3D structure and packing of such a long sequence cannot be left to pure chance, as DNA must be efficiently used for its primary roles as a matrix for transcription and replication. In recent years, methods like chromatin conformation capture (including 3C, 4C, Hi-C, ChIA-PET and Multi-ChIA) and optical microscopy have advanced substantially and have shed new light on how eukaryotic genomes are hierarchically organized; first into 10-nm fiber, next into DNA loops, topologically associated domains and finally into interphase or mitotic chromosomes. This knowledge has allowed us to revise our understanding regarding the mechanisms governing the process of DNA organization. Mounting experimental evidence suggests that the key element in the formation of loops is the binding of the CCCTC-binding factor (CTCF) to DNA; a protein that can be referred to as the chief organizer of the genome. However, CTCF does not work alone but in cooperation with other proteins, such as cohesin or Yin Yang 1 (YY1). In this short review, we briefly describe our current understanding of the structure of eukaryotic genomes, how they are established and how the formation of DNA loops can influence gene expression. We discuss the recent discoveries describing the 3D structure of the CTCF-DNA complex and the role of CTCF in establishing genome structure. Finally, we briefly explain how various genetic disorders might arise as a consequence of mutations in the CTCF target sequence or alteration of genomic imprinting.

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Cancer is an exceedingly complex disease that is orchestrated and driven by a combination of multiple aberrantly regulated processes. The nature and depth of involvement of individual events vary between cancer types, and in lung cancer, the deregulation of the epigenetic machinery, the tumor microenvironment and the immune system appear to be especially relevant. The contribution of microRNAs to carcinogenesis and cancer progression is well established with many reports and investigations describing the involvement of microRNAs in lung cancer, however most of these studies have concentrated on single microRNA-target relations and have not adequately addressed the complexity of their interactions. In this review, we focus, in part, on the role of microRNAs in the epigenetic regulation of lung cancer where they act as active molecules modulating enzymes that take part in methylation-mediated silencing and chromatin remodeling. Additionally, we highlight their contribution in controlling and modulating the tumor microenvironment and finally, we describe their role in the critical alteration of essential molecules that influence the immune system in lung cancer development and progression.

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Root hairs are tubular outgrowths of specialized epidermal cells called trichoblasts. They affect anchoring plants in soil, the uptake of water and nutrients and are the sites of the interaction between plants and microorganisms. Nineteen root hair mutants of barley representing different stages of root hair development were subjected to detailed morphological and genetic analyses. Each mutant was monogenic and recessive. An allelism test revealed that nine loci were responsible for the mutated root hair phenotypes in the collection and 1-4 mutated allelic forms were identified at each locus. Genetic relationships between the genes responsible for different stages of root hair formation were established. The linkage groups of four loci rhl1, rhp1, rhi1 and rhs1, which had previously been mapped on chromosomes 7H, 1H, 6H and 5H, respectively, were enriched with new markers that flank the genes at a distance of 0.16 cM to 4.6 cM. The chromosomal position of three new genes - two that are responsible for the development of short root hairs (rhs2 and rhs3) and the gene that controls an irregular root hair pattern (rhi2) - were mapped on chromosomes 6H, 2H and 1H, respectively. A comparative analysis of the agrobotanical parameters between some mutants and their respective parental lines showed that mutations in genes responsible for root hair development had no effect on the agrobotanical performance of plants that were grown under controlled conditions. The presented mutant collection is a valuable tool for further identification of genes controlling root hair development in barley.

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The prevalence of JAK2V617F tyrosine kinase mutation differs between various variants of myelofibrosis with the higher detection rate for patients with post-polycythemia vera myelofibrosis (post-PV MF; 91%) if compared to primary myelofibrosis (PMF; 45%) and post-essential thrombocythemia myelofibrosis (post-ET MF; 39%). The impact of V617F point mutation and its allele burden on overall survival (OS) and the risk of leukemic transformation (LT) has been the subject of several studies, but the results were ambiguous. Our study included 77 patients with the following variants: 42 patients with PMF (55%), 16 with post-ET MF (21%) and 19 with post-PV MF (24%). Median age at diagnosis for the entire cohort was 61 years (range 19-81), with 53% of female. A total of 42 patients were JAK2V617F positive, giving an overall frequency of 55%; the median allele burden was 22% (range 2-96%). The JAK2V617F point mutation was detected in 21 patients with PMF (50%), 14 with post-PV MF (88%) and 7 with post-ET MF (37%). Lower JAK2V617F allele burden was more frequently detected in PMF patients, whereas higher allele burden was predominantly seen in post-PV/ET MF group. There was no significant difference between V617F-positive and V617F-negative patients in terms of studied parameters in PMF as well as in post-PV/ET MF subgroup. No significant difference was also demonstrated when the above-mentioned subpopulations were analyzed according to JAK2V617F allele burden, except higher leukocyte count in post-PV/ET MF patients with higher allele burden (14.3×10(9)/L vs. 6.2×10(9)/L; p=.03). Median follow-ups for V617F-positive and V617F-negative patients were 16.6 months (range 3.6-206.4) and 36.4 months (range 2.5-142.1), respectively. The presence of JAK2V617F mutation did not affect OS and the risk of LT development.

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Infection thread-dependent invasion of legume roots by rhizobia leads to internalization of bacteria into the plant cells, which is one of the salient features of root nodule symbiosis. We found that two genes, Nap1 (for Nck-associated protein 1) and Pir1 (for 121F-specific p53 inducible RNA), involved in actin rearrangements were essential for infection thread formation and colonization of Lotus japonicus roots by its natural microsymbiont, Mesorhizobium loti. nap1 and pir1 mutants developed an excess of uncolonized nodule primordia, indicating that these two genes were not essential for the initiation of nodule organogenesis per se. However, both the formation and subsequent progression of infection threads into the root cortex were significantly impaired in these mutants. We demonstrate that these infection defects were due to disturbed actin cytoskeleton organization. Short root hairs of the mutants had mostly transverse or web-like actin filaments, while bundles of actin filaments in wild-type root hairs were predominantly longitudinal. Corroborating these observations, temporal and spatial differences in actin filament organization between wild-type and mutant root hairs were also observed after Nod factor treatment, while calcium influx and spiking appeared unperturbed. Together with various effects on plant growth and seed formation, the nap1 and pir1 alleles also conferred a characteristic distorted trichome phenotype, suggesting a more general role for Nap1 and Pir1 in processes establishing cell polarity or polar growth in L. japonicus.

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