Synergistic activation of the tumor suppressor, HLJ1, by the transcription factors YY1 and activator protein 1

Chi Chung Wang, Meng Feng Tsai, Ting Hao Dai, Tse Ming Hong, Wing Kai Chan, Jeremy J.W. Chen, Pan Chyr Yang

Research output: Contribution to journalArticle

44 Citations (Scopus)


HLJ1 is a novel tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. However, the mechanism of HLJ1 activation is currently unclear. Here, we identify an enhancer segment in the HLJ1 gene at -2,125 to -1,039 bp upstream of the transcription start site. A 50-bp element between -1,492 and -1,443 bp is the minimal enhancer segment, which includes the activator protein 1 (AP-1) site (-1,457 to -1,451 bp), an essential regulatory domain that binds the transcriptional factors FosB, JunB, and JunD. Chromatin immunoprecipitation assays confirm that these AP-1 family members bind to a specific site in the HLJ1 enhancer segment in vivo. Overexpression of either YY1 at promoter or AP-1 at enhancer results in a 3-fold increase in the transcriptional activity of HLJ1. We propose a novel mechanism whereby expression of the tumor suppressor, HLJ1, is upregulated via enhancer AP-1 binding to promoter YY1 and the coactivator, p300, through DNA bending and multiprotein complex formation. The combined expression of AP-1 and YY1 enhances HLJ1 expression by more than five times and inhibits in vitro cancer cell invasion. Elucidation of the regulatory mechanism of HLJ1 expression may facilitate the development of personalized therapy by inhibiting cancer cell proliferation, angiogenesis, and metastasis.

Original languageEnglish
Pages (from-to)4816-4826
Number of pages11
JournalCancer Research
Issue number10
Publication statusPublished - 2007 May 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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