Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells

Christopher D. Scharer, Colleen D. McCabe, Mohamed Ali-Seyed, Michael F. Berger, Martha L. Bulyk, Carlos S. Moreno

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

SOX4 is a critical developmental transcription factor in vertebrates and is required for precise differentiation and proliferation in multiple tissues. In addition, SOX4 is overexpressed in many human malignancies, but the exact role of SOX4 in cancer progression is not well understood. Here, we have identified the direct transcriptional targets of SOX4 using a combination of genome-wide localization chromatin immunoprecipitation-chip analysis and transient overexpression followed by expression profiling in a prostate cancer model cell line. We have also used protein-binding microarrays to derive a novel SOX4-specific position-weight matrix and determined that SOX4 binding sites are enriched in SOX4-bound promoter regions. Direct transcriptional targets of SOX4 include several key cellular regulators, such as EGFR, HSP70, Tenascin C, Frizzled-5, Patched-1, and Delta-like 1. We also show that SOX4 targets 23 transcription factors, such as MLL, FOXA1, ZNF281, and NKX3-1. In addition, SOX4 directly regulates expression of three components of the RNA-induced silencing complex, namely Dicer, Argonaute 1, and RNA Helicase A. These data provide new insights into how SOX4 affects developmental signaling pathways and how these changes may influence cancer progression via regulation of gene networks involved in microRNA processing, transcriptional regulation, the TGFβ, Wnt, Hedgehog, and Notch pathways, growth factor signaling, and tumor metastasis.

Original languageEnglish
Pages (from-to)709-717
Number of pages9
JournalCancer Research
Volume69
Issue number2
DOIs
Publication statusPublished - 15 Jan 2009
Externally publishedYes

Fingerprint

Gene Regulatory Networks
Prostatic Neoplasms
Genome
Neoplasms
Transcription Factors
RNA-Induced Silencing Complex
Position-Specific Scoring Matrices
RNA Helicases
Tenascin
Protein Array Analysis
Hedgehogs
Chromatin Immunoprecipitation
MicroRNAs
Genetic Promoter Regions
Protein Binding
Vertebrates
Intercellular Signaling Peptides and Proteins
Binding Sites
Neoplasm Metastasis
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Scharer, C. D., McCabe, C. D., Ali-Seyed, M., Berger, M. F., Bulyk, M. L., & Moreno, C. S. (2009). Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells. Cancer Research, 69(2), 709-717. https://doi.org/10.1158/0008-5472.CAN-08-3415

Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells. / Scharer, Christopher D.; McCabe, Colleen D.; Ali-Seyed, Mohamed; Berger, Michael F.; Bulyk, Martha L.; Moreno, Carlos S.

In: Cancer Research, Vol. 69, No. 2, 15.01.2009, p. 709-717.

Research output: Contribution to journalArticle

Scharer, CD, McCabe, CD, Ali-Seyed, M, Berger, MF, Bulyk, ML & Moreno, CS 2009, 'Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells', Cancer Research, vol. 69, no. 2, pp. 709-717. https://doi.org/10.1158/0008-5472.CAN-08-3415
Scharer, Christopher D. ; McCabe, Colleen D. ; Ali-Seyed, Mohamed ; Berger, Michael F. ; Bulyk, Martha L. ; Moreno, Carlos S. / Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells. In: Cancer Research. 2009 ; Vol. 69, No. 2. pp. 709-717.
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