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

► Enhanced at Puberty 1 (EAP1) is an upper-echelon transcriptional regulator of puberty and reproductive function. ► Transcription of EAP1 mRNA is initiated at a preferred Transcription Start Site. ► The EAP1 promoter is activated by two transcription factors, TTF1 and CUX1-p200. ► The EAP1 promoter...

Full description

Saved in:
Bibliographic Details
Published in:Molecular and cellular endocrinology 2012-04, Vol.351 (2), p.184-198
Main Authors: Mueller, Johanna K., Koch, Ines, Lomniczi, Alejandro, Loche, Alberto, Rulfs, Tomke, Castellano, Juan M., Kiess, Wieland, Ojeda, Sergio, Heger, Sabine
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cell Line
chromatin
Chromatin Immunoprecipitation
DNA
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
EAP1
Female
Gene expression
Gene Expression Regulation
Gene Regulatory Networks
Genes, Regulator - genetics
Genes, Tumor Suppressor
gonadotropin-releasing hormone
Gonadotropin-Releasing Hormone - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
hypothalamus
Hypothalamus - metabolism
Hypothalamus - physiology
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
neurons
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
precipitin tests
Promoter Regions, Genetic
Puberty
Puberty - genetics
Rats
Rats, Sprague-Dawley
Regulatory Sequences, Nucleic Acid
reporter genes
repressor proteins
Repressor Proteins - genetics
Repressor Proteins - metabolism
secretion
Securin
Transcription
transcription (genetics)
Transcription Factors
Transcription, Genetic
tumor suppressor genes
YY1 Transcription Factor - genetics
YY1 Transcription Factor - metabolism
zinc finger motif
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:► Enhanced at Puberty 1 (EAP1) is an upper-echelon transcriptional regulator of puberty and reproductive function. ► Transcription of EAP1 mRNA is initiated at a preferred Transcription Start Site. ► The EAP1 promoter is activated by two transcription factors, TTF1 and CUX1-p200. ► The EAP1 promoter is repressed by EAP1 itself, YY1 and CUX1-p110. ► All four transcription factors are recruited in vivo to the EAP1 promoter. 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 2744bp) 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.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2011.12.004