title: Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
abstract: Steroidogenic Factor-1 (SF-1) is a nuclear receptor that has a pivotal role in the development of adrenal glands and gonads and in the control of steroid hormone production, being also implicated in the pathogenesis of adrenocortical tumors. We have analyzed the mechanisms how SF-1 controls gene expression in adrenocortical cells and showed that it regulates different categories of genes according to its dosage. Significant correlations exist between the localization of SF-1-binding sites in chromatin under different dosage conditions and dosage-dependent regulation of gene expression. Our study revealed unexpected functional interactions between SF-1 and Neuron-Restrictive Silencer Factor/RE1-Silencing Transcription Factor (NRSF/REST), which was first characterized as a repressor of neuronal gene expression in non-neuronal tissues, in the regulation of gene expression in steroidogenic cells. When overexpressed, SF-1 reshapes the repertoire of NRSF/REST-regulated genes, relieving repression of key steroidogenic genes. These data show that NRSF/REST has a novel function in regulating gene expression in steroidogenic cells and suggest that it may have a broad role in regulating tissue-specific gene expression programs.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire CNRS, Valbonne 06560, France, Associated International Laboratory (LIA) NEOGENEX CNRS, Valbonne 06560, France, University of Nice-Sophia-Antipolis, Valbonne 06560, France, Federal University of Paraná, Curitiba, Paraná 80060-000, Brazil, Instituto de Pesquisa Pelé Pequeno Principe, Curitiba, Paraná 80250-060, Brazil and Department of Oncology, University of Turin, Orbassano 10043, Italy.
authors.forename: Mabrouka
authors.initials: M
authors.lastname: Doghman
authors.forename: Bonald C
authors.initials: BC
authors.lastname: Figueiredo
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D012097:Repressor Proteins / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D002843:Chromatin; D004247:DNA; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D000099229:RE1-Silencing Transcription Factor
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