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

Ferraz-de-Souza, Bruno, Lin, Lin, Shah, Sonia, Jina, Nipurna, Hubank, Mike, Dattani, Mehul T. and Achermann, John C. (2011) 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. FASEB Journal, 25 4: 1166-1175. doi:10.1096/fj.10-170522


Author Ferraz-de-Souza, Bruno
Lin, Lin
Shah, Sonia
Jina, Nipurna
Hubank, Mike
Dattani, Mehul T.
Achermann, John C.
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
Journal name FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
1530-6860
Publication date 2011-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1096/fj.10-170522
Open Access Status DOI
Volume 25
Issue 4
Start page 1166
End page 1175
Total pages 10
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Language eng
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.
Keyword Adrenal development
Adrenal tumorigenesis
Angiogenesis
NCI-H295R adrenocortical cells
Transcriptional regulation
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID G0700089
4798066
079666
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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