Phosphorylated C/EBPβ influences a complex network involving YY1 and USF2 in lung epithelial cells

Victoria Viart; Jessica Varilh; Estelle Lopez; Céline René; Mireille Claustres; Magali Taulan-Cadars

doi:10.1371/journal.pone.0060211

Phosphorylated C/EBPβ influences a complex network involving YY1 and USF2 in lung epithelial cells

PLoS One. 2013;8(4):e60211. doi: 10.1371/journal.pone.0060211. Epub 2013 Apr 1.

Authors

Victoria Viart¹, Jessica Varilh, Estelle Lopez, Céline René, Mireille Claustres, Magali Taulan-Cadars

Affiliation

¹ UFR de Médecine, Université Montpellier1, Montpellier, France ; INSERM U827, Laboratoire de Génétique de Maladies Rares, Montpellier, France.

Abstract

The promoter of the cystic fibrosis transmembrane conductance regulator gene CFTR is tightly controlled by regulators including CCAAT/enhancer binding proteins (C/EBPs). We previously reported that the transcription factors YY1 and USF2 affect CFTR expression. We can now demonstrate that C/EBPβ, a member of the CCAAT family, binds to the CFTR promoter and contributes to its transcriptional activity. Our data reveal that C/EBPβ cooperates with USF2 and acts antagonistically to YY1 in the control of CFTR expression. Interestingly, YY1, a strong repressor, fails to repress the CFTR activation induced by USF2 through DNA binding competition. Collectively, the data strongly suggest a model by which USF2 functionally interacts with YY1 blocking its inhibitory activity, in favour of C/EBPβ transactivation. Further investigation into the interactions between these three proteins revealed that phosphorylation of C/EBPβ influences the DNA occupancy of YY1 and favours the interaction between USF2 and YY1. This phosphorylation process has several implications in the CFTR transcriptional process, thus evoking an additional layer of complexity to the mechanisms influencing CFTR gene regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Binding Sites
CCAAT-Enhancer-Binding Protein-beta / genetics
CCAAT-Enhancer-Binding Protein-beta / metabolism*
Cell Line
Cystic Fibrosis Transmembrane Conductance Regulator / genetics
Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
Epithelial Cells / cytology
Epithelial Cells / metabolism*
Gene Expression Regulation*
Genes, Reporter
Humans
Luciferases
Molecular Sequence Data
Phosphorylation
Promoter Regions, Genetic
Protein Binding
Respiratory Mucosa / cytology
Respiratory Mucosa / metabolism*
Signal Transduction
Transcription, Genetic
Upstream Stimulatory Factors / genetics
Upstream Stimulatory Factors / metabolism*
YY1 Transcription Factor / genetics
YY1 Transcription Factor / metabolism*

Substances

CCAAT-Enhancer-Binding Protein-beta
CEBPB protein, human
CFTR protein, human
USF2 protein, human
Upstream Stimulatory Factors
YY1 Transcription Factor
YY1 protein, human
Cystic Fibrosis Transmembrane Conductance Regulator
Luciferases

Grants and funding

This work was supported by grants from Vaincre la Mucoviscidose, Université Montpellier 1, Hopital Arnaud de Villeneuve/CHU Montpellier, and the Inserm Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.