Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding

Repression of the cellular CIITA gene is part of the immune evasion strategy of the γherpes virus Epstein-Barr virus (EBV) during its lytic replication cycle in B-cells. In part this is mediated through down regulation of MHC class II gene expression via the targeted repression of CIITA, the cellular master regulator of MHC class II gene expression. The repression is achieved through a reduction in CIITA promoter activity initiated by the EBV transcription and replication factor Zta (BZLF1, EB1, ZEBRA). Zta is the earliest gene expressed during the lytic replication cycle. Zta interacts with sequence specific elements in promoters, enhancers and the replication origin (ZREs) and also modulates gene expression through interaction with cellular transcription factors and co-activators. Here we explore the requirements for Zta-mediated repression of the CIITA promoter. We find that repression by Zta is specific for the CIITA promoter and can be achieved in the absence of other EBV genes. Surprisingly, we find that the dimerization region of Zta is not required to mediate repression. This contrasts with an obligate requirement of this region to correctly orientate the DNA contact regions of Zta to mediate activation of gene expression through ZREs. Additional support for the model that Zta represses the CIITA promoter without direct DNA binding comes from promoter mapping that shows that repression does not require the presence of a ZRE in the CIITA promoter

Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers.

International audienceGerm-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still not fully understood. We report here the involvement of miR-146a and miR-146b-5p that bind to the same site in the 3'UTR of BRCA1 and down-regulate its expression as demonstrated using reporter assays. This was further confirmed with the endogenous BRCA1 gene by transfecting microRNA (miRNA) precursors or inhibitors in mammary cell lines. This down-regulation was accompanied by an increased proliferation and a reduced homologous recombination rate, two processes controlled by BRCA1. Furthermore, we showed that the highest levels of miR-146a and/or miR-146b-5p are found in basal-like mammary tumour epithelial cell lines and in triple negative breast tumours, which are the closest to tumours arising in carriers of BRCA1 mutations. This work provides further evidence for the involvement of miRNAs in sporadic breast cancer through down-regulation of BRCA1

Contrasting trends between species and catchments in diadromous fish counts over the last 30 years in France

The decline and collapse of populations have been reported for a large range of taxa. Diadromous fishes migrate between fresh water and the sea and encounter many anthropogenic pressures during their complex life cycle. In spite of being of ecological, cultural and economic interest, diadromous fishes have been in decline for decades in many parts across the world. In this study, we investigated the change in five diadromous fish counts in France over a 30-year period using 43 monitoring stations located in 29 rivers across 18 catchments. Our hypothesis was that the counts of these species evolved in a contrasting way between catchments. We also tested the effect of five drivers potentially contributing to the observed trends: catchment, latitude, presence of commercial fisheries, improvement of ecological continuity and salmon stocking. We found contrasting trends in fish counts between species at the national scale, with some taxa increasing (Anguilla anguilla and Salmo trutta), some showing a slight increase (Salmo salar) and some decreasing (Alosa spp. and Petromyzon marinus). For each taxon, except Anguilla anguilla, we highlighted a significant catchment effect indicating contrasting trends between catchments and stations. However, we found no significant effect of catchment characteristics for any of the studied taxa

Diadromous fish modified timing of upstream migration over the last 30 years in France

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