Transcription of the Geminin Gene is Regulated by a Negative-feedback Loop

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2014 Feb 21

PMID 24554762

Citations 4

Authors

Yoshinori Ohno

Keita Saeki

Shinichiro Yasunaga

Toshiaki Kurogi

Kyoko Suzuki-Takedachi

Manabu Shirai

Keichiro Mihara

Kenichi Yoshida

J Willem Voncken

Motoaki Ohtsubo

Yoshihiro Takihara

Affiliations

Soon will be listed here.

Abstract

Geminin performs a central function in regulating cellular proliferation and differentiation in development and also in stem cells. Of interest, down-regulation of Geminin induces gene transcription regulated by E2F, indicating that Geminin is involved in regulation of E2F-mediated transcriptional activity. Because transcription of the Geminin gene is reportedly regulated via an E2F-responsive region (E2F-R) located in the first intron, we first used a reporter vector to examine the effect of Geminin on E2F-mediated transcriptional regulation. We found that Geminin transfection suppressed E2F1- and E2F2-mediated transcriptional activation and also mildly suppressed such activity in synergy with E2F5, 6, and 7, suggesting that Geminin constitutes a negative-feedback loop for the Geminin promoter. Of interest, Geminin also suppressed nuclease accessibility, acetylation of histone H3, and trimethylation of histone H3 at lysine 4, which were induced by E2F1 overexpression, and enhanced tri-methylation of histone H3 at lysine 27 and monoubiquitination of histone H2A at lysine 119 in E2F-R. However, Geminin5EQ, which does not interact with Brahma or Brg1, did not suppress accessibility to nuclease digestion or transcription but had an overall dominant-negative effect. These findings suggest that E2F-mediated activation of Geminin transcription is negatively regulated by Geminin through the inhibition of chromatin remodeling.

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