HTLV-1 HBZ cooperates with JunD to enhance transcription of the human telomerase reverse transcriptase gene (hTERT)

<p>Abstract</p> <p>Background</p> <p>Activation of telomerase is a critical and late event in tumor progression. Thus, in patients with adult-T cell leukaemia (ATL), an HTLV-1 (Human T cell Leukaemia virus type 1)-associated disease, leukemic cells display a high telomerase activity, mainly through transcriptional up-regulation of the human telomerase catalytic subunit (hTERT). The HBZ (HTLV-1 bZIP) protein coded by the minus strand of HTLV-1 genome and expressed in ATL cells has been shown to increase the transcriptional activity of JunD, an AP-1 protein. The presence of several AP-1 binding sites in the hTERT promoter led us to investigate whether HBZ regulates hTERT gene transcription.</p> <p>Results</p> <p>Here, we demonstrate using co-transfection assays that HBZ in association with JunD activates the hTERT promoter. Interestingly, the -378/+1 proximal region, which does not contain any AP-1 site was found to be responsible for this activation. Furthermore, an increase of hTERT transcripts was observed in cells co-expressing HBZ and JunD. Chromatin immunoprecipitation (ChIP) assays revealed that HBZ, and JunD coexist in the same DNA-protein complex at the proximal region of hTERT promoter. Finally, we provide evidence that HBZ/JunD heterodimers interact with Sp1 transcription factors and that activation of hTERT transcription by these heterodimers is mediated through GC-rich binding sites for Sp1 present in the proximal sequences of the hTERT promoter.</p> <p>Conclusion</p> <p>These observations establish for the first time that HBZ by intervening in the re-activation of telomerase, may contribute to the development and maintenance of the leukemic process.</p

Combining farmers' decision rules and landscape stochastic regularities for landscape modelling

International audienceLandscape spatial organization (LSO) strongly impacts many environmental issues. Modelling agricultural landscapes and describing meaningful landscape patterns are thus regarded as key-issues for designing sustainable landscapes. Agricultural landscapes are mostly designed by farmers. Their decisions dealing with crop choices and crop allocation to land can be generic and result in landscape regularities, which determine LSO. This paper comes within the emerging discipline called "landscape agronomy", aiming at studying the organization of farming practices at the landscape scale. We here aim at articulating the farm and the landscape scales for landscape modelling. To do so, we develop an original approach consisting in the combination of two methods used separately so far: the identification of explicit farmer decision rules through on-farm surveys methods and the identification of landscape stochastic regularities through data-mining. We applied this approach to the Niort plain landscape in France. Results show that generic farmer decision rules dealing with sunflower or maize area and location within landscapes are consistent with spatiotemporal regularities identified at the landscape scale. It results in a segmentation of the landscape, based on both its spatial and temporal organization and partly explained by generic farmer decision rules. This consistency between results points out that the two modelling methods aid one another for land-use modelling at landscape scale and for understanding the driving forces of its spatial organization. Despite some remaining challenges, our study in landscape agronomy accounts for both spatial and temporal dimensions of crop allocation: it allows the drawing of new spatial patterns coherent with land-use dynamics at the landscape scale, which improves the links to the scale of ecological processes and therefore contributes to landscape ecology.L'organisation du paysage influe sur les problèmes environnementaux. Modéliser les paysages pour les décrire à l'aide de formes significatives est une étage clé. Les paysages agricoles sont principalement construits par les agriculteurs dont les décision d'assolement peuvent être génériques et déterminer des régularités dans l'organisation du paysage. Cet article contribue à l'agronomie des paysage qui est une discipline émergente. Nous cherchons à articuler les échelles du paysage et de l'exploitation agricole en développant deux méthodes : l'une consiste à identifier les décisions des agriculteurs par le bais d'enquêtes, l'autre consiste à retrouver des régularités stochastiques dans le paysage par le bais de fouille de données. Nous avons appliqué cette approche au paysage de la plaine de Niort en France. Les résultats montrent que les décisions des agriculteurs en matière de tournesol et maïs sont génériques et ont des effets sur le paysages que des méthodes de fouille de données révèlent et quantifient

La répression des gènes cibles directs sparc et collagène alpha2(I) par l'oncoprotéine v-Jun au cours de la transformation (un nouveau mécanisme qui implique les facteurs de transcription ubiquitaires SP1et Sp3)

LYON-ENS Sciences (693872304) / SudocSudocFranceF

LA REPRESSION DE LA PROTEINE DE MATRICE EXTRACELLULAIRE SPARC AU COURS DE LA TRANSFORMATION PAR VJUN (ROLE PHYSIOLOGIQUE ET MECANISME MOLECULAIRE)

LYON-ENS Sciences (693872304) / SudocSudocFranceF

LA TRANSFORMATION INDUITE PAR L'ONCOPROTEINE VJUN (ISOLEMENT DE GENES CIBLES ET MISE EN EVIDENCE DU POTENTIEL TRANSFORMANT DU FACTEUR DE TRANSCRIPTION ATF3)

LYON-ENS Sciences (693872304) / SudocSudocFranceF