Class-C Sox transcription factors control GnRH gene expression via the intronic transcriptional enhancer

Hee Dae Kim, Han Kyoung Choe, Sooyoung Chung, Myungjin Kim, Jae Young Seong, Gi Hoon Son, Kyungjin Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

GnRH is a pivotal hypothalamic neurohormone governing reproduction and sexual development. Because transcriptional regulation is crucial for the spatial and temporal expression of the GnRH gene, a region approximately 3.0 kb upstream of the mammalian GnRH promoter has been extensive studied. In the present study, we demonstrate a transcription-enhancer located in the first intron (intron A) region of the GnRH gene. This transcriptional enhancer harbors putative sex-determining region Y-related high-mobility-group box (SOX) family transcription factorbinding sites, which are well conserved across many mammalian species. The class-C SOX member proteins (SOX-C) (SOX4 and SOX11) specifically augment this transcriptional activation by binding to these SOX-binding sites. In accordance, SOX11 is highly enriched in immortalized GnRH-producing GT1-1 cells, and suppression of its expression significantly decreases GnRH gene expression as well as GnRH secretion. Chromatin immunoprecipitation shows that endogenous SOX-C factors recognize and bind to the intronic enhancer in GT1-1 cells and the hypothalamus. Accompanying immunohistochemical analysis demonstrates that SOX4 or SOX11 are highly expressed in the majority of hypothalamic GnRH neurons in adult mice. Taken together, these findings demonstrate that SOX-C transcription factors function as important transcriptional regulators of cell type-specific GnRH gene expression by acting on the intronic transcriptional enhancer.

Original languageEnglish
Pages (from-to)1184-1196
Number of pages13
JournalMolecular Endocrinology
Volume25
Issue number7
DOIs
Publication statusPublished - 2011 Jul 1

Fingerprint

Gonadotropin-Releasing Hormone
Transcription Factors
Gene Expression
SOX Transcription Factors
Introns
Sexual Development
Chromatin Immunoprecipitation
Protein C
Transcriptional Activation
Hypothalamus
Reproduction
Neurotransmitter Agents
Binding Sites
Neurons
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Class-C Sox transcription factors control GnRH gene expression via the intronic transcriptional enhancer. / Kim, Hee Dae; Choe, Han Kyoung; Chung, Sooyoung; Kim, Myungjin; Seong, Jae Young; Son, Gi Hoon; Kim, Kyungjin.

In: Molecular Endocrinology, Vol. 25, No. 7, 01.07.2011, p. 1184-1196.

Research output: Contribution to journalArticle

Kim, Hee Dae ; Choe, Han Kyoung ; Chung, Sooyoung ; Kim, Myungjin ; Seong, Jae Young ; Son, Gi Hoon ; Kim, Kyungjin. / Class-C Sox transcription factors control GnRH gene expression via the intronic transcriptional enhancer. In: Molecular Endocrinology. 2011 ; Vol. 25, No. 7. pp. 1184-1196.
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