Academic Commons

Articles

Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing

Nakhla, Atif; Hryb, Daniel; Rosner, William; Romas, Nicholas A.; Xiang, Zhaoying; Kahn, Scott M.

Human sex hormone-binding globulin (SHBG) regulates free sex steroid concentrations in plasma and modulates rapid, membrane based steroid signaling. SHBG is encoded by an eight exon-long transcript whose expression is regulated by a downstream promoter (PL). The SHBG gene was previously shown to express a second major transcript of unknown function, derived from an upstream promoter (PT), and two minor transcripts. We report that transcriptional expression of the human SHBG gene is far more complex than previously described. PL and PT direct the expression of at least six independent transcripts each, resulting from alternative splicing of exons 4, 5, 6, and/or 7. We mapped two transcriptional start sites downstream of PL and PT, and present evidence for a third SHBG gene promoter (PN) within the neighboring FXR2 gene; PN regulates the expression of at least seven independent SHBG gene transcripts, each possessing a novel, 164-nt first exon (1N). Transcriptional expression patterns were generated for human prostate, breast, testis, liver, and brain, and the LNCaP, MCF-7, and HepG2 cell lines. Each expresses the SHBG transcript, albeit in varying abundance. Alternative splicing was more pronounced in the cancer cell lines. PL- PT- and PN-derived transcripts were most abundant in liver, testis, and prostate, respectively. Initial findings reveal the existence of a smaller immunoreactive SHBG species in LNCaP, MCF-7, and HepG2 cells. These results extend our understanding of human SHBG gene transcription, and raise new and important questions regarding the role of novel alternatively spliced transcripts, their function in hormonally responsive tissues including the breast and prostate, and the role that aberrant SHBG gene expression may play in cancer.

Subjects

Files

  • thumnail for 1471-2199-10-37-S1.DOC 1471-2199-10-37-S1.DOC binary/octet-stream 25.5 KB Download File
  • thumnail for a421fa31ed48e5b2b9c8d37b8264ef13.zip a421fa31ed48e5b2b9c8d37b8264ef13.zip binary/octet-stream 772 KB Download File

Also Published In

Title
BMC Molecular Biology
DOI
https://doi.org/10.1186/1471-2199-10-37

More About This Work

Academic Units
Medicine
Urology
Publisher
BioMed Central
Published Here
September 8, 2014
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.