title: Computational identification of potential transcriptional regulators of TGF-ß1 in human atherosclerotic arteries.
abstract: TGF-ß is protective in atherosclerosis but deleterious in metastatic cancers. Our aim was to determine whether TGF-ß transcriptional regulation is tissue-specific in early atherosclerosis. The computational methods included 5 steps: (i) from microarray data of human atherosclerotic carotid tissue, to identify the 10 best co-expressed genes with TGFB1 (TGFB1 gene cluster), (ii) to choose the 11 proximal promoters, (iii) to predict the TFBS shared by the promoters, (iv) to identify the common TFs co-expressed with the TGFB1 gene cluster, and (v) to compare the common TFs in the early lesions to those identified in advanced atherosclerotic lesions and in various cancers. Our results show that EGR1, SP1 and KLF6 could be responsible for TGFB1 basal expression, KLF6 appearing specific to atherosclerotic lesions. Among the TFs co-expressed with the gene cluster, transcriptional activators (SLC2A4RG, MAZ) and repressors (ZBTB7A, PATZ1, ZNF263) could be involved in the fine-tuning of TGFB1 expression in atherosclerosis.
authors.affiliation: EA 4173 Génomique Fonctionnelle de l'Hypertension Artérielle, Université de Lyon, Université Lyon 1, Hôpital Nord-Ouest Villefranche-sur-Saône, 8 avenue Rockefeller, F-69373 Lyon, France; Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Université de Carthage, Faculté des Sciences de Bizerte, Bizerte, Tunisia.
authors.forename: Nedra
authors.initials: N
authors.lastname: Dhaouadi
authors.affiliation: EA 4173 Génomique Fonctionnelle de l'Hypertension Artérielle, Université de Lyon, Université Lyon 1, Hôpital Nord-Ouest Villefranche-sur-Saône, 8 avenue Rockefeller, F-69373 Lyon, France.
authors.forename: Jacques-Yuan
authors.initials: JY
authors.lastname: Li
authors.affiliation: EA 4173 Génomique Fonctionnelle de l'Hypertension Artérielle, Université de Lyon, Université Lyon 1, Hôpital Nord-Ouest Villefranche-sur-Saône, 8 avenue Rockefeller, F-69373 Lyon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Feugier
authors.affiliation: EA 4173 Génomique Fonctionnelle de l'Hypertension Artérielle, Université de Lyon, Université Lyon 1, Hôpital Nord-Ouest Villefranche-sur-Saône, 8 avenue Rockefeller, F-69373 Lyon, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Gustin
authors.affiliation: Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Université de Carthage, Faculté des Sciences de Bizerte, Bizerte, Tunisia.
authors.forename: Houcine
authors.initials: H
authors.lastname: Dab
authors.affiliation: Unité de Physiologie Intégrée, Laboratoire de Pathologies Vasculaires, Université de Carthage, Faculté des Sciences de Bizerte, Bizerte, Tunisia.
authors.forename: Kamel
authors.initials: K
authors.lastname: Kacem
authors.affiliation: EA 4173 Génomique Fonctionnelle de l'Hypertension Artérielle, Université de Lyon, Université Lyon 1, Hôpital Nord-Ouest Villefranche-sur-Saône, 8 avenue Rockefeller, F-69373 Lyon, France.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Bricca
authors.affiliation: EA 4173 Génomique Fonctionnelle de l'Hypertension Artérielle, Université de Lyon, Université Lyon 1, Hôpital Nord-Ouest Villefranche-sur-Saône, 8 avenue Rockefeller, F-69373 Lyon, France. Electronic address: cerutti@univ-lyon1.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cerutti
mesh_terms: D001665:Binding Sites; D002339:Carotid Arteries / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000378:metabolism*; D002478:Cells, Cultured; D003198:Computer Simulation; D051766:Early Growth Response Protein 1 / Q000502:physiology; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000502:physiology; D008957:Models, Genetic; D005810:Multigene Family; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Atherosclerosis; Gene co-expression; Microarray; Transcriptome; Transforming growth factor-beta 1; Vascular smooth muscle cells