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Many plant processes depend on differential gene expression, which is generally controlled by complex proteins called transcription factors (TFs). In peach, 1533 TFs have been identified, accounting for about 5.5% of the 27,852 protein-coding genes. These TFs are the reference for the rest of the Prunus species. TF studies in Prunus have been performed on the gene expression analysis of different agronomic traits, including control of the flowering process, fruit quality, and biotic and abiotic stress resistance. These studies, using quantitative RT-PCR, have mainly been performed in peach, and to a lesser extent in other species, including almond, apricot, black cherry, Fuji cherry, Japanese apricot, plum, and sour and sweet cherry. Other tools have also been used in TF studies, including cDNA-AFLP, LC-ESI-MS, RNA, and DNA blotting or mapping. More recently, new tools assayed include microarray and high-throughput DNA sequencing (DNA-Seq) and RNA sequencing (RNA-Seq). New functional genomics opportunities include genome resequencing and the well-known synteny among Prunus genomes and transcriptomes. These new functional studies should be applied in breeding programs in the development of molecular markers. With the genome sequences available, some strategies that have been used in model systems (such as SNP genotyping assays and genotyping-by-sequencing) may be applicable in the functional analysis of Prunus TFs as well. In addition, the knowledge of the gene functions and position in the peach reference genome of the TFs represents an additional advantage. These facts could greatly facilitate the isolation of genes via QTL (quantitative trait loci) map-based cloning in the different Prunus species, following the association of these TFs with the identified QTLs using the peach reference genome. ; This study has been supported by the projects AGL2010-16335 and AGL2013-43550-R from the Spanish Ministry of Economy and Competiveness to MR and PMG and in part by the Ministero delle Politiche Agricole Alimentari e Forestali–Italy (MiPAAF www.politicheagricole.it) through the project "DRUPOMICS" (grant DM14999/7303/08) to CB, LT, and IV. The authors would like to thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)—Ministério da Educação (Brazil) for the fellowship (BEX9514/13-9) supporting the stay of VB in Spain. ; Peer reviewed ; Peer Reviewed

Almost 30 years ago pioneering work by the laboratories of Harald von Boehmer and Susumo Tonegawa provided the first indications that developing thymocytes could assemble a functional TCRβ chain-containing receptor complex, the pre-TCR, before TCRα expression. The discovery and study of the pre-TCR complex revealed paradigms of signaling pathways in control of cell survival and proliferation, and culminated in the recognition of the multifunctional nature of this receptor. As a receptor integrated in a dynamic developmental process, the pre-TCR must be viewed not only in the light of the biological outcomes it promotes, but also in context with those molecular processes that drive its expression in thymocytes. This review article focuses on transcription factors and target genes activated by the pre-TCR to drive its different outcomes. ; Work in CL-R and JA laboratory has been supported by the Ramón y Cajal and I3 Researchers Programs (CL-R), research grants from the Spanish Government (SAF2009-08066, SAF2012-36535 to CL-R; and BFU2008-01070, SAF2011-24268 to JA), Fundació la Marató TV3 (080730, 122530 to CL-R and JA), the Marie Curie International Reintegration Program of the European Union (MCIRG516308 to CL-R), the Spanish Ministry of Health (ISCIII-RETIC RD06/0009-FEDER), and Generalitat de Catalunya (2009SGR601, 2014SGR1153). CL-R is a recipient of the ICREA Acadèmia Award (Generalitat de Catalunya).

The transcriptional response driven by Hypoxia-inducible factor (HIF) is central to the adaptation to oxygen restriction. Despite recent characterization of genome-wide HIF DNA binding locations and hypoxia-regulated transcripts in different cell types, the molecular bases of HIF target selection remain unresolved. Herein, we combined multi-level experimental data and computational predictions to identify sequence motifs that may contribute to HIF target selectivity. We obtained a core set of bona fide HIF binding regions by integrating multiple HIF1 DNA binding and hypoxia expression profiling datasets. This core set exhibits evolutionarily conserved binding regions and is enriched in functional responses to hypoxia. Computational prediction of enriched transcription factor binding sites identified sequence motifs corresponding to several stress-responsive transcription factors, such as activator protein 1 (AP1), cAMP response element-binding (CREB), or CCAAT-enhancer binding protein (CEBP). Experimental validations on HIF-regulated promoters suggest a functional role of the identified motifs in modulating HIF-mediated transcription. Accordingly, transcriptional targets of these factors are over-represented in a sorted list of hypoxia-regulated genes. Altogether, our results implicate cooperativity among stress-responsive transcription factors in fine-tuning the HIF transcriptional response ; This work was supported by Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation, MICINN) [grant number SAF2008-03147 to L. del P.], Comunidad Autónoma de Madrid [grant number S-SAL-0311_2006 to L. del P.] and the 7th Research Framework Programme of the European Union [grant number METOXIA project ref. HEALTH-F2-2009-222741] to L. del P. D.V. was a recipient of PhD funding from the Spanish Ministry of Science and Innovation [FPU programme] and the European Molecular Biology Organization [Short-Term Fellowships]

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al. ; The transcriptional response driven by Hypoxia-inducible factor (HIF) is central to the adaptation to oxygen restriction. Despite recent characterization of genome-wide HIF DNA binding locations and hypoxia-regulated transcripts in different cell types, the molecular bases of HIF target selection remain unresolved. Herein, we combined multi-level experimental data and computational predictions to identify sequence motifs that may contribute to HIF target selectivity. We obtained a core set of bona fide HIF binding regions by integrating multiple HIF1 DNA binding and hypoxia expression profiling datasets. This core set exhibits evolutionarily conserved binding regions and is enriched in functional responses to hypoxia. Computational prediction of enriched transcription factor binding sites identified sequence motifs corresponding to several stress-responsive transcription factors, such as activator protein 1 (AP1), cAMP response element-binding (CREB), or CCAAT-enhancer binding protein (CEBP). Experimental validations on HIF-regulated promoters suggest a functional role of the identified motifs in modulating HIF-mediated transcription. Accordingly, transcriptional targets of these factors are over-represented in a sorted list of hypoxia-regulated genes. Altogether, our results implicate cooperativity among stress-responsive transcription factors in fine-tuning the HIF transcriptional response. ; This work was supported by Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation, MICINN) [grant number SAF2008-03147 to L. del P.], Comunidad Autónoma de Madrid [grant number S-SAL-0311_2006 to L. del P.] and the 7th Research Framework Programme of the European Union [grant number METOXIA project ref. HEALTH-F2-2009-222741] to L. del P. D.V. was a recipient of PhD funding from the Spanish Ministry of Science and Innovation [FPU programme] and the European Molecular Biology Organization [Short-Term Fellowships]. ; Peer reviewed

Statistical models of promoter architecture are presented. Key transcription factors associated with housekeeping expression are identified. ; LH was funded to perform this work by the National Science Centre, Poland, grant POLONEZ 2 (grant number 2016/21/P/NZ2/03926). This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 665778. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

In gene regulation, transcription factors (TFs) play a key function. It transmits genetic information from DNA to messenger RNA during the process of DNA transcription. During this step, the transcription factor binds to a segment of the DNA sequence known as Transcription Factor Binding Sites (TFBS). The goal of this study is to build a model that predicts whether or not a DNA binding site attaches to a certain transcription factor (TF). TFs are regulatory molecules that bind to particular sequence motifs in the gene to induce or restrict targeted gene transcription. Two classification methods will be used, which are support vector machine (SVM) and kernel logistic regression (KLR). Moreover, the KLR algorithm depends on another regression algorithm, namely kernel ridge regression (KRR). Discovering binding sites for a transcription factor can help determine genes which it regulates, analyze its functions, comprehend regulation in living organisms, recognize causal disease variations, and, most importantly, manufacture pharmaceutical drugs.

El pdf es el manuscrito de autor. ; Vitamin D receptor (VDR) mediates the antitumoral action of the active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). However, VDR expression is lost during colon cancer progression, possibly causing unresponsiveness to 1,25(OH)2D3. Although several mechanisms responsible for resistance to 1,25(OH)2D3 action in different types of cancer had been reported, none explained the loss of VDR expression. We have found that the transcription factors Snail1 and Snail2, known as inducers of epithelial-to-mesenchymal transition (EMT), inhibit VDR expression and block 1,25(OH)2D3 action in colon cancer cells. Snail1 and Snail2 have an additive repressing effect on VDR gene promoter. These effects are specific to the Snail family, as other transcription factors that function as EMT inducers do not inhibit VDR expression in colon cancer cells. Moreover, we also found that the RNA expression of SNAI1 and SNAI2 is upregulated in human colorectal tumors and inversely correlates with that of VDR. Our results suggest that high levels of SNAIL1 and SNAIL2 are a probable cause of VDR downregulation and 1,25(OH)2D3 unresponsiveness in colon cancer. In addition, they may contribute to the improvement of protocols for the clinical use of vitamin D compounds, as they indicate that advanced colon cancer patients overexpressing SNAIL1 and SNAIL2 are not suitable candidates for this therapy. © 2010 Elsevier Ltd. ; The work in authors' laboratories is supported by the Ministerio de Ciencia e Innovación of Spain (SAF2007-60341, ISCIII-RETIC RD06/0020/0009 and RD06/0020/0020), Comunidad de Madrid (S-GEN-0266/2006) and European Union (MRTN-CT-2005-019496, NucSys). ; Peer Reviewed

Access to genome-wide data provides the opportunity to address questions concerning the ability of transcription factors (TFs) to assemble in distinct macromolecular complexes. Here, we introduce the PAnDA (Protein And DNA Associations) approach to characterize DNA associations with human TFs using expression profiles, protein-protein interactions and recognition motifs. Our method predicts TF binding events with >0.80 accuracy revealing cell-specific regulatory patterns that can be exploited for future investigations. Even when the precise DNA-binding motifs of a specific TF are not available, the information derived from protein-protein networks is sufficient to perform high-confidence predictions (area under the ROC curve of 0.89). PAnDA is freely available at http://service.tartaglialab.com/new_submission/panda. ; The research leading to these results has received funding from the European Research Council under the European/nUnion's Seventh Framework Programme (FP7/2007-2013)/ ERC grant agreementRIBOMYLOME 309545; the Fundació La Marató de TV3 (20142731); and the Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013-2017' (SEV-2012-0208). Funding for Open Access charge: European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement RIBOMYLOME 309545 and Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013-2017' (SEV-2012-0208).

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. ; The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. The induction of the AER is a complex process that relies on integrated interactions among the Fgf, Wnt, and Bmp signaling pathways that operate within the ectoderm and between the ectoderm and the mesoderm of the early limb bud. The transcription factors Sp6 and Sp8 are expressed in the limb ectoderm and AER during limb development. Sp6 mutant mice display a mild syndactyly phenotype while Sp8 mutants exhibit severe limb truncations. Both mutants show defects in AER maturation and in dorsal-ventral patterning. To gain further insights into the role Sp6 and Sp8 play in limb development, we have produced mice lacking both Sp6 and Sp8 activity in the limb ectoderm. Remarkably, the elimination or significant reduction in Sp6;Sp8 gene dosage leads to tetra-amelia; initial budding occurs, but neither Fgf8 nor En1 are activated. Mutants bearing a single functional allele of Sp8 (Sp6−/−;Sp8+/−) exhibit a split-hand/foot malformation phenotype with double dorsal digit tips probably due to an irregular and immature AER that is not maintained in the center of the bud and on the abnormal expansion of Wnt7a expression to the ventral ectoderm. Our data are compatible with Sp6 and Sp8 working together and in a dose-dependent manner as indispensable mediators of Wnt/ßcatenin and Bmp signaling in the limb ectoderm. We suggest that the function of these factors links proximal-distal and dorsal-ventral patterning. ; Supported by grant BFU2011-24972 from the Spanish Government (MAR) and by National Organization of Rare Diseases (KCO) and by the Intramural Research Program at the National Institute of Dental and Craniofacial Research, NIH, USA (YY). ; Peer Reviewed

Eucalypts are the most planted trees worldwide, but most of them are frost sensitive. Overexpressing transcription factors for CRT-repeat binding factors (CBFs) in transgenic Eucalyptus confer cold resistance both in leaves and stems. While wood plays crucial roles in trees and is affected by environmental cues, its potential role in adaptation to cold stress has been neglected. Here, we addressed this question by investigating the changes occurring in wood in response to the overexpression of two CBFs, taking advantage of available transgenic Eucalyptus lines. We performed histological, biochemical, and transcriptomic analyses on xylem samples. CBF ectopic expression led to a reduction of both primary and secondary growth, and triggered changes in xylem architecture with smaller and more frequent vessels and fibers exhibiting reduced lumens. In addition, lignin content and syringyl/guaiacyl (S/G) ratio increased. Consistently, many genes of the phenylpropanoid and lignin branch pathway were upregulated. Most of the features of xylem remodeling induced by CBF overexpression are reminiscent of those observed after long exposure of Eucalyptus trees to chilling temperatures. Altogether, these results suggest that CBF plays a central role in the cross-talk between response to cold and wood formation and that the remodeling of wood is part of the adaptive strategies to face cold stress. ; The Centre National pour la Recherche Scientifique (CNRS), the University Paul Sabatier Toulouse III (UPS), the French MERI (Ministry of Education, Research and Innovation), and the French Laboratory of Excellence project 'TULIP'(ANR-10-LABX-41; ANR-11-IDEX-0002-02). This research was also financially supported by the Vietnamese government for PhD grants (P.B. Cao and C. Nguyen). ; http://www.mdpi.com/journal/ijms ; hj2020 ; Biochemistry ; Forestry and Agricultural Biotechnology Institute (FABI) ; Genetics ; Microbiology and Plant Pathology

15 páginas.-- 7 figuras.-- 53 referencias.-- The online version of this article (doi:10.1007/s00425-015-2336-y) contains supplementary material, which is available to authorized users. ; Main conclusion Transcription factors normally expressed in sunflower seeds delayed vegetative senescence induced by severe stress in transgenic tobacco. This revealed a novel connection between seed heat shock factors, desiccation tolerance and vegetative longevity. HaHSFA9 and HaHSFA4a coactivate a genetic program that, in sunflower (Helianthus annuus L.), contributes to seed longevity and desiccation tolerance. We have shown that overexpression of HaHSFA9 in transgenic tobacco seedlings resulted in tolerance to drastic dehydration and oxidative stress. Overexpression of HaHSFA9 alone was linked to a remarkable protection of the photosynthetic apparatus. In addition, the combined overexpression of HaHSFA9 and HaHSFA4a enhanced all these stress-resistance phenotypes. Here, we find that HaHSFA9 confers protection against damage induced by different stress conditions that accelerate vegetative senescence during different stages of development. Seedlings and plants that overexpress HaHSFA9 survived lethal treatments of dark-induced senescence. HaHSFA9 overexpression induced resistance to effects of culture under darkness for several weeks. Only some homoiochlorophyllous resurrection plants are able to withstand this experimental severe stress condition. The combined overexpression of HaHSFA9 and HaHSFA4a did not result in further slowing of dark-induced seedling senescence. However, combined expression of the two transcription factors caused improved recovery of the photosynthetic organs of seedlings after lethal dark treatments. At later stages of vegetative development, HaHSFA9 delayed the appearance of senescence symptoms in leaves of plants grown under normal illumination. This delay was observed under either control or stress treatments. Thus, HaHSFA9 delayed both natural and stress-induced leaf senesce. These novel observations connect transcription factors involved in desiccation tolerance with leaf longevity. ; This work was supported by the European Regional Development Fund (FEDER) and the Spanish Secretary of Research, Development, and Innovation (Grants BIO2011-23440). Some additional funds came from the Andalusian Regional Government (Grant BIO148). ; Peer reviewed

[EN] Nitric oxide (NO) is an important signaling compound in prokaryotes and eukaryotes. In plants, NO regulates critical developmental transitions and stress responses. Here, we identify a mechanism for NO sensing that coordinates responses throughout development based on targeted degradation of plant-specific transcriptional regulators, the group VII ethylene response factors (ERFs). We show that the N-end rule pathway of targeted proteolysis targets these proteins for destruction in the presence of NO, and we establish them as critical regulators of diverse NO-regulated processes, including seed germination, stomatal closure, and hypocotyl elongation. Furthermore, we define the molecular mechanism for NO control of germination and crosstalk with abscisic acid (ABA) signaling through ERF-regulated expression of ABSCISIC ACID INSENSITIVE5 (ABI5). Our work demonstrates how NO sensing is integrated across multiple physiological processes by direct modulation of transcription factor stability and identifies group VII ERFs as central hubs for the perception of gaseous signals in plants. ; M.J.H., S.P.P., D.J.G., G.M.M., J.V.C., and C.S.C. were supported by UK Biotechnology and Biological Sciences Research Council (BBSRC) grants BB/G02488X/1, BB/G010595/1, BB/F006934/1, and BB/K000144/1 (including financial support from SAB Miller plc); J.E.G. was supported by BB/K000063/1; N.M.I. by a MARA PhD fellowship from the Malaysian government; S.B. by a University of Nottingham PhD fellowship; and M.M. by a University of Sheffield Faculty of Science Studentship. D.J.G. was supported by a Nottingham Advanced Research Fellowship for part of this work. J.L.-J., A.C., and J.L. were supported by grants CSD2007-00057 and BIO2011-27526 from the Spanish government. G.W.B. was supported by a Marie Curie IIF Fellowship. The work of A.B. was supported by the Austrian Science foundation FWF (grants P21215 and P25488). Rothamsted Research receives grant-aided support from the BBSRC. D.F.A.T. and J.B. were funded by BBSRC grant ...