Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions.

BackgroundCTCF and BORIS (CTCFL), two paralogous mammalian proteins sharing nearly identical DNA binding domains, are thought to function in a mutually exclusive manner in DNA binding and transcriptional regulation.ResultsHere we show that these two proteins co-occupy a specific subset of regulatory elements consisting of clustered CTCF binding motifs (termed 2xCTSes). BORIS occupancy at 2xCTSes is largely invariant in BORIS-positive cancer cells, with the genomic pattern recapitulating the germline-specific BORIS binding to chromatin. In contrast to the single-motif CTCF target sites (1xCTSes), the 2xCTS elements are preferentially found at active promoters and enhancers, both in cancer and germ cells. 2xCTSes are also enriched in genomic regions that escape histone to protamine replacement in human and mouse sperm. Depletion of the BORIS gene leads to altered transcription of a large number of genes and the differentiation of K562 cells, while the ectopic expression of this CTCF paralog leads to specific changes in transcription in MCF7 cells.ConclusionsWe discover two functionally and structurally different classes of CTCF binding regions, 2xCTSes and 1xCTSes, revealed by their predisposition to bind BORIS. We propose that 2xCTSes play key roles in the transcriptional program of cancer and germ cells

The epigenetic factor BORIS/CTCFL regulates the NOTCH3 gene expression in cancer cells.

Aberrant upregulation of NOTCH3 gene plays a critical role in cancer pathogenesis. However, the underlying mechanisms are still unknown. We tested here the hypothesis that aberrant epigenetic modifications in the NOTCH3 promoter region might account for its upregulation in cancer cells. We compared DNA and histone methylation status of NOTCH3 promoter region in human normal blood cells and T cell acute lymphoblastic leukemia (T-ALL) cell lines, differentially expressing NOTCH3. We found that histone methylation, rather than DNA hypomethylation, contributes towards establishing an active chromatin status of NOTCH3 promoter in NOTCH3 overexpressing cancer cells. We discovered that the chromatin regulator protein BORIS/CTCFL plays an important role in regulating NOTCH3 gene expression. We observed that BORIS is present in T-ALL cell lines as well as in cell lines derived from several solid tumors overexpressing NOTCH3. Moreover, BORIS targets NOTCH3 promoter in cancer cells and it is able to induce and to maintain a permissive/active chromatin conformation. Importantly, the association between NOTCH3 overexpression and BORIS presence was confirmed in primary T-ALL samples from patients at the onset of the disease. Overall, our results provide novel insights into the determinants of NOTCH3 overexpression in cancer cells, by revealing a key role for BORIS as the main mediator of transcriptional deregulation of NOTCH3. Copyright © 2014 Elsevier B.V. All rights reserved

Стилістичний аспект ідеологічного дискурсу Бориса Джонсона під час його першої промови як Прем’єр-міністра, 24.07.09

The following work is focused on the problem of the Stylistic devices and Expressive means usage within the Boris Johnsons’ first speech as a Prime Minister of the UK, 07.24.19, to realize his pragmatic purposes. The first speech of Boris Johnsons is defined as political, institutional, ideological discourse to promote the idea of Brexit among the population of the UK as the most relevant idea for the given community. It is stated that all the language inventory in the form of Stylistic devices and Expressive means used within the Boris Johnsons’ first speech as a Prime Minister of the UK serves to influence the addressee to accept the idea of Brexit as the only one way for the better life in the UK. It is stressed that the author of message uses a great number of epithets to show the benefits of Brexit. Metaphors used in the message are considered not only to appeal to the feelings, emotions of the addressee, but to provoke thinking about the described objects, subjects and phenomena. It is underlined that parallel constructions in the form of anaphora and epiphora within the speech of Boris Johnsons are able to make the information more stressed and valuable. Parenthetic sentences and detachments used in the message are determined as means to give some additional information, some arguments for Brexit, as well as means to express Boris Johnsons’ attitude to the described events and facts. It is pointed out that polysyndeton, asyndeton within the Boris Johnsons speech are used to arrest addressee’s attention to the enumerated items. The usage of polysyndetons and asyndetons within the limited space of speech is defined as specific feature of Boris Johnsons’ first speech as a Prime Minister of the UK, as the means to strike addressee, to etch the given information in the addressee’s memory. It is stated that all used Stylistic devices and Expressive means within the Boris Johnsons’ first speech as a Prime Minister of the UK serve not only to realize speaker’ s pragmatic purposes, but they represent the idiolect and form the idiostyle of Boris Johnsons, as well as create the textual ornament of the given message.У дослідженні cфокусовано увагу на використанні стилістичних прийомів та виразових засобів у першій промові Бориса Джонсона як Прем’єр-міністра Об’єднаного Королівства від 24.07.19. з метою реалізації своїх прагматичних намірів. Перша промова Бориса Джонсона визначена як політичний, інституційний, ідеологічний дискурс – просування ідеї Брекзиту серед населення Об’єднаного Королівства як найбільш релевантної для цієї спільноти. Стверджено, що весь мовний інвентар, тобто стилістичні прийоми та виразові засоби першої промови Бориса Джонсона, слугує впливу на адресата для визнання ним ідеї Брекзиту як єдиного способу покращити життя в Об’єднаному Королівстві. Підкреслено, що промовець послуговується великою кількістю епітетів для демонстрації переваг Брекзиту. З’ясовано, що метафори, використані у повідомленні, не тільки апелюють до емоцій та почуттів адресата, але й здатні провокувати думки щодо зображених об’єктів, суб’єктів, явищ; паралельні конструкції у фор- мі епіфори та анафори перетворюють інформацію на більш виразну та ціннісну; вставні речення та конструкції сприяють наданню детальнішої інформації та аргументів щодо Брекзиту, а також є способом для Бориса Джонсона висловити своє ставлення до зображуваних подій та фактів. Визначено, що використання в промові полісиндетона та асиндетона є особливою рисою виступу Бориса Джонсона як Прем’єр-міністра Об’єднаного Королівства, засобом здивувати адресата та закарбувати в його пам’яті подану інформацію. Підсумовано, що всі стилістичні прийоми та виразові засоби слугують не тільки для реалізації прагматичних цілей промовця, але й репрезентують його ідеолект та формують його ідіостиль, а також створюють текстовий орнамент поданого повідомлення

Dostoevsky\u27s (translated by Boris Jakim) The Insulted and Injured (Book Review)

A Review of The Insulted and Injured, by Fyodor Dostoevsky, translated by Boris Jakim. Grand Rapids, MI: Eerdmans, 2011. 368 pp. $18.00; ISBN 9780802825902

High Expression of hTERT and Stemness Genes in BORIS/CTCFL Positive Cells Isolated from Embryonic Cancer Cells.

BORIS/CTCFL is a member of cancer testis antigen family normally expressed in germ cells. In tumors, it is aberrantly expressed although its functions are not completely well-defined. To better understand the functions of BORIS in cancer, we selected the embryonic cancer cells as a model. Using a molecular beacon, which specifically targets BORIS mRNA, we demonstrated that BORIS positive cells are a small subpopulation of tumor cells (3-5% of total). The BORIS-positive cells isolated using BORIS-molecular beacon, expressed higher telomerase hTERT, stem cell (NANOG, OCT4, SOX2) and cancer stem cell marker genes (CD44 and ALDH1) compared to the BORIS-negative tumor cells. In order to define the functional role of BORIS, stable BORIS-depleted embryonic cancer cells were generated. BORIS silencing strongly down-regulated the expression of hTERT, stem cell and cancer stem cell marker genes. Moreover, the BORIS knockdown increased cellular senescence in embryonic cancer cells, revealing a putative role of BORIS in the senescence biological program. Our data indicate an association of BORIS expressing cells subpopulation with the expression of stemness genes, highlighting the critical role played by BORIS in embryonic neoplastic disease

CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention

The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but the molecular details of this process remain unclear. Here, we demonstrate that a 79-aa region within the CTCF N terminus is essential for cohesin positioning at CTCF binding sites and chromatin loop formation. However, the N terminus of CTCF fused to artificial zinc fingers was not sufficient to redirect cohesin to non-CTCF binding sites, indicating a lack of an autonomously functioning domain in CTCF responsible for cohesin positioning. BORIS (CTCFL), a germline-specific paralog of CTCF, was unable to anchor cohesin to CTCF DNA binding sites. Furthermore, CTCF-BORIS chimeric constructs provided evidence that, besides the N terminus of CTCF, the first two CTCF zinc fingers, and likely the 3D geometry of CTCF-DNA complexes, are also involved in cohesin retention. Based on this knowledge, we were able to convert BORIS into CTCF with respect to cohesin positioning, thus providing additional molecular details of the ability of CTCF to retain cohesin. Taken together, our data provide insight into the process by which DNA-bound CTCF constrains cohesin movement to shape spatiotemporal genome organization

Russian investment abroad. The basic flows and features

This paper is one of several studies done at the Hungarian Academy of Sciences ’ Insti-tute for World Economics ((IWE) under the CIS Strategic Research Project. A contract between the Hungarian Prime Minister's Office and the Hungarian Academy of Sciences in the summer of 2007, allowed some new, wide-ranging thematic research into the post-Soviet space to be launched. The project entitled “Hungary’s CIS strategy with special regard to Russia, Ukraine and Kazakhstan ” gave new impetus to post-Soviet research in the IWE and its partner the Hungarian Academy of Sciences ’ Research In-stitute of Sociology. The new opportunity was important especially because the CIS or post-Soviet space had become a neglected area in Hungary over the previous 15 years and there was a research gap to fill. Meanwhile the post-Soviet space has been returning to the political agenda in the last year or two, due to rising ambitions in a strengthened Russia, sharp conflicts within the post-Soviet space, and worldwide problems of energy supply and prices. The research seeks to provide up-to-date answers to such emerging questions. The project sets out to cover a wide range of essential issues about the CIS space