title: ChIP-on-chip analysis reveals angiopoietin 2 (Ang2, ANGPT2) as a novel target of steroidogenic factor-1 (SF-1, NR5A1) in the human adrenal gland.
abstract: The nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) is a key regulator of adrenal and gonadal biology. Disruption of SF-1 can lead to disorders of adrenal development, while increased SF-1 dosage has been associated with adrenocortical tumorigenesis. We aimed to identify a novel subset of SF-1 target genes in the adrenal by using chromatin immunoprecipitation (ChIP) microarrays (ChIP-on-chip) combined with systems analysis. SF-1 ChIP-on-chip was performed in NCI-H295R human adrenocortical cells using promoter tiling arrays, leading to the identification of 445 gene loci where SF-1-binding regions were located from 10 kb upstream to 3 kb downstream of a transcriptional start. Network analysis of genes identified as putative SF-1 targets revealed enrichment for angiogenic process networks. A 1.1-kb SF-1-binding region was identified in the angiopoietin 2 (Ang2, ANGPT2) promoter in a highly repetitive region, and SF-1-dependent activation was confirmed in luciferase assays. Angiogenesis is paramount in adrenal development and tumorigenesis, but until now a direct link between SF-1 and vascular remodeling has not been established. We have identified Ang2 as a potentially important novel target of SF-1 in the adrenal gland, indicating that regulation of angiogenesis might be an important additional mechanism by which SF-1 exerts its actions in the adrenal gland.
authors.affiliation: Developmental Endocrinology Research Group, UCL Institute of Child Health, University College London, London, UK.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ferraz-de-Souza
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Sonia
authors.initials: S
authors.lastname: Shah
authors.forename: Nipurna
authors.initials: N
authors.lastname: Jina
authors.forename: Mike
authors.initials: M
authors.lastname: Hubank
authors.forename: Mehul T
authors.initials: MT
authors.lastname: Dattani
authors.forename: John C
authors.initials: JC
authors.lastname: Achermann
mesh_terms: D000230:Adenocarcinoma; D000310:Adrenal Gland Neoplasms; D000311:Adrenal Glands / Q000196:embryology / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000235:genetics*; D001665:Binding Sites / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; C486381:CITED2 protein, human; C515057:NR5A1 protein, human; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D015534:Trans-Activators