Transcription of the human EAP1 gene is regulated by upstream components of a puberty-controlling Tumor Suppressor Gene network

Johanna K. Mueller, Ines Koch, Alejandro Lomniczi, Alberto Loche, Tomke Rulfs, Juan M. Castellano, Wieland Kiess, Sergio Ojeda, Sabine Heger

    Research output: Contribution to journalArticle

    19 Scopus citations

    Abstract

    Mammalian puberty is initiated by an increased pulsatile release of gonadotropin-releasing hormone (GnRH) from specialized neurons located in the hypothalamus. GnRH secretion is controlled by neuronal and glial networks, whose activity appears to be coordinated via transcriptional regulation. One of the transcription factors involved in this process is thought to be the recently described gene Enhanced at Puberty 1 (EAP1), which encodes a protein with dual transcriptional activity. In this study we used gene reporter and chromatin immunoprecipitation (ChIP) assays to examine the hypothesis that EAP1 expression is controlled by transcriptional regulators earlier postulated to serve as central nodes of a gene network involved in the neuroendocrine control of puberty. These regulators include Thyroid Transcription Factor 1 (TTF1), Yin Yang 1 (YY1), and CUX1, in addition to EAP1 itself. While TTF1 has been shown to facilitate the advent of puberty, YY1 (a zinc finger protein component of the Polycomb silencing complex) may play a repressive role. The precise role of CUX1 in this context is not known, but like EAP1, CUX1 can either activate or repress gene transcription. We observed that DNA segments of two different lengths (998 and 2744. bp) derived from the 5'-flanking region of the human EAP1 gene display similar transcriptional activity. TTF1 stimulates transcription from both DNA segments with equal potency, whereas YY1, CUX1, and EAP1 itself, behave as transcriptional repressors. All four proteins are recruited in vivo to the EAP1 5'-flanking region. These observations suggest that EAP1 gene expression is under dual transcriptional regulation imposed by a trans-activator (TTF1) and two repressors (YY1 and CUX1) previously postulated to be upstream components of a puberty-controlling gene network. In addition, EAP1 itself appears to control its own expression via a negative auto-feedback loop mechanism. Further studies are needed to determine if the occupancy of the EAP1 promoter by these regulatory factors changes at the time of puberty.

    Original languageEnglish (US)
    Pages (from-to)184-198
    Number of pages15
    JournalMolecular and Cellular Endocrinology
    Volume351
    Issue number2
    DOIs
    StatePublished - Apr 4 2012

    Keywords

    • EAP1
    • Gene expression
    • Puberty
    • Transcription

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Endocrinology

    Fingerprint Dive into the research topics of 'Transcription of the human EAP1 gene is regulated by upstream components of a puberty-controlling Tumor Suppressor Gene network'. Together they form a unique fingerprint.

  • Cite this