JPO1/CDCA7, a novel transcription factor E2F1-induced protein, possesses intrinsic transcriptional regulator activity

Yuya Goto1, Reiko Hayashi, Tomoki Muramatsu

  • 1Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan.

Insights

JPO1/CDCA7 is identified as a direct transcriptional target of transcription factor E2F1. This finding reveals JPO1/CDCA7 as a unique transcription regulator activated by both E2F1 and c-Myc.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cancer Biology

Background:

  • JPO1/CDCA7 was previously identified as a c-Myc-responsive gene involved in neoplastic transformation.
  • The precise regulatory mechanisms controlling JPO1/CDCA7 expression were not fully elucidated.

Purpose of the Study:

  • To identify JPO1/CDCA7 as a direct transcriptional target of the E2F1 transcription factor.
  • To characterize the role of E2F1 in regulating JPO1/CDCA7 gene expression and its functional domains.

Main Methods:

  • Adenoviral-mediated gene transfer to overexpress E2F1 in human cells.
  • Analysis of JPO1/CDCA7 promoter constructs in human and mouse cells.
  • Mammalian one-hybrid assay to assess transcriptional activity.
  • Chromatin immunoprecipitation (ChIP) assays to determine E2F protein binding.

Main Results:

  • E2F1 overexpression upregulated JPO1/CDCA7 mRNA levels.
  • An E2F-responsive sequence in the JPO1/CDCA7 promoter was essential for E2F1-induced transcription.
  • E2F1, E2F2, and E2F4 bound to the JPO1/CDCA7 promoter.
  • The C-terminal region of JPO1/CDCA7 protein exhibited transcriptional activity.

Conclusions:

  • JPO1/CDCA7 is a direct transcriptional target of E2F1.
  • JPO1/CDCA7 functions as a unique transcription regulator, with its expression activated by both E2F1 and c-Myc.

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