Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/48423
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dc.titleNFIC REGULATES AR MEDIATED TRANSCRIPTION BY MULTIPLE MECHANISMS
dc.contributor.authorYANG CHONG
dc.date.accessioned2013-12-04T18:00:06Z
dc.date.available2013-12-04T18:00:06Z
dc.date.issued2013-08-01
dc.identifier.citationYANG CHONG (2013-08-01). NFIC REGULATES AR MEDIATED TRANSCRIPTION BY MULTIPLE MECHANISMS. ScholarBank@NUS Repository.
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/48423
dc.description.abstractAndrogen receptor (AR) has been shown to play a key role in mediating the transcriptional regulatory network directing prostate cancer initiation, development and progression. To gain insights into the AR-dependent transcriptional regulatory network, we utilized the ChIP-Seq approach and generated genome-wide binding maps of AR in the LNCaP prostate cancer cell line. From our bioinformatic analyses of AR binding sites (ARBS), we found an enrichment of motifs belonging to the NFI family. We demonstrated that a member of the NFI family, NFIC, shown to be over-expressed in clinical prostate tumors, overlaps with a large fraction of ARBS across the genome. Our analysis revealed that the recruitment of NFIC was independent of androgen treatment, indicating NFIC as a potential pioneer factor. In addition, we showed that NFIC was required for the global modulation of AR-dependent target genes including KLK2, KLK3, and TMPRSS2. Interestingly, we found another well characterized AR pioneering factor, FoxA1, to be recruited to the ARBS associated with these genes. However, the expressions of these genes were FoxA1 independent, suggesting NFIC was the more important pioneering factor at these ARBS. We hypothesized that NFIC and FoxA1 could co-pioneer AR and went on to demonstrate that NFIC and FoxA1 played distinct roles globally for different classes of AR modulated genes and their associated ARBS. Collectively, our study suggests NFIC is a novel pioneering factor that is complementary to FoxA1 in AR-mediated transcription.
dc.language.isoen
dc.subjectNFIC,Androgen Receptor, Prsotate cancer, transcriptional regulation
dc.typeThesis
dc.contributor.departmentNUS GRAD SCH FOR INTEGRATIVE SCI & ENGG
dc.contributor.supervisorYONG EU LEONG
dc.contributor.supervisorEDWIN CHEUNG CHONG WING
dc.description.degreePh.D
dc.description.degreeconferredDOCTOR OF PHILOSOPHY
dc.identifier.isiutNOT_IN_WOS
Appears in Collections:Ph.D Theses (Open)

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