title: A comprehensive nuclear receptor network for breast cancer cells.
abstract: In breast cancer, nuclear receptors (NRs) play a prominent role in governing gene expression, have prognostic utility, and are therapeutic targets. We built a regulatory map for 24 NRs, six chromatin state markers, and 14 breast-cancer-associated transcription factors (TFs) that are expressed in the breast cancer cell line MCF-7. The resulting network reveals a highly interconnected regulatory matrix where extensive crosstalk occurs among NRs and other breast -cancer-associated TFs. We show that large numbers of factors are coordinately bound to highly occupied target regions throughout the genome, and these regions are associated with active chromatin state and hormone-responsive gene expression. This network also provides a framework for stratifying and predicting patient outcomes, and we use it to show that the peroxisome proliferator-activated receptor delta binds to a set of genes also regulated by the retinoic acid receptors and whose expression is associated with poor prognosis in breast cancer.
authors: Institute of Genomics and Systems Biology, Argonne National Laboratory, Chicago, IL 60637, USA.
authors: Ralf
authors: R
authors: Kittler
authors: Jie
authors: J
authors: Zhou
authors: Sujun
authors: S
authors: Hua
authors: Lijia
authors: L
authors: Ma
authors: Yuwen
authors: Y
authors: Liu
authors: Elisha
authors: E
authors: Pendleton
authors: Chao
authors: C
authors: Cheng
authors: Mark
authors: M
authors: Gerstein
authors: Kevin P
authors: KP
authors: White
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002843:Chromatin / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D061986:MCF-7 Cells; D047494:PPAR delta / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D047494:PPAR delta; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors