Cooperative control via lymphoid enhancer factor 1/T cell factor 3 and estrogen receptor-α for uterine gene regulation by estrogen

Sanhita Ray, Fuhua Xu, Haibin Wang, Sanjoy K. Das

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Accumulating evidence indicates that estrogen regulates diverse but interdependent signaling pathways via estrogen receptor (ER)-dependent and -independent mechanisms. However, molecular relationship between these pathways for gene regulation under the direction of estrogen remains unknown. To address this possibility, our uterine analysis of Wnt/β-catenin downstream effectors revealed that lymphoid enhancer factor 1 (Lef-1) and T cell factor 3 (Tcf-3) are up-regulated temporally by 17β-estradiol (E2) in an ER-independent manner. Lef-1 is abundantly up-regulated early (within 2 h), whereas Tcf-3 is predominantly induced after 6 h, and both are sustained through 24 h. Interestingly, activated Lef-1/Tcf-3 molecularly interacted with ERα in a time-dependent manner, suggesting they possess a cross talk in the uterus by E2. Moreover, dual immunofluorescence studies confirm their colocalization in uterine epithelial cells after E2. Most importantly, using chromatin immunoprecipitation followed by PCR analyses, we provide evidence for an interesting possibility that ERα and Tcf-3/Lef-1 complex occupies at certain DNA regions of estrogen-responsive endogenous gene promoters in the mouse uterus. By selective perturbation of activated Lef-1/Tcf-3 or ERα signaling events, we provide in this study novel evidence that cooperative interactions, by these two different classes of transcription factors at the level of chromatin, direct uterine regulation of estrogen-responsive genes. Collectively, these studies support a mechanism that integration of a nonclassically induced β-catenin/Lef-1/Tcf-3 signaling with ERα is necessary for estrogen-dependent endogenous gene regulation in uterine biology.

Original languageEnglish (US)
Pages (from-to)1125-1140
Number of pages16
JournalMolecular Endocrinology
Volume22
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Transcription Factor 7-Like 1 Protein
TCF Transcription Factors
Estrogen Receptors
Estrogens
Genes
Catenins
Uterus
Chromatin Immunoprecipitation
Chromatin
Fluorescent Antibody Technique
Estradiol
Transcription Factors
Epithelial Cells
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Cooperative control via lymphoid enhancer factor 1/T cell factor 3 and estrogen receptor-α for uterine gene regulation by estrogen. / Ray, Sanhita; Xu, Fuhua; Wang, Haibin; Das, Sanjoy K.

In: Molecular Endocrinology, Vol. 22, No. 5, 05.2008, p. 1125-1140.

Research output: Contribution to journalArticle

Ray, Sanhita ; Xu, Fuhua ; Wang, Haibin ; Das, Sanjoy K. / Cooperative control via lymphoid enhancer factor 1/T cell factor 3 and estrogen receptor-α for uterine gene regulation by estrogen. In: Molecular Endocrinology. 2008 ; Vol. 22, No. 5. pp. 1125-1140.
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