Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors

Carolyn M. Klinge, Sarah Jernigan, K. A. Mattingly, K. E. Risinger, J. Zhang

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

One mechanism by which ligand-activated estrogen receptors α and β (ERα and ERβ) stimulate gene transcription is through direct ER interaction with specific DNA sequences, estrogen response elements (EREs). ERE-bound ER recruits coactivators that stimulate gene transcription. Binding of ER to natural and synthetic EREs with different nucleotide sequences alters ER binding affinity, conformation, and transcriptional activity, indicating that the ERE sequence is an allosteric effector of ER action. Here we tested the hypothesis that alterations in ER conformation induced by binding to different ERE sequences modulates ER interaction with coactivators and corepressors. CHO-K1 cells transfected with ERα or ERβ show ERE sequence-dependent differences in the functional interaction of ERα and ERβ with coactivators steroid receptor coativator 1 (SRC-1), SRC-2 (glucocorticoid receptor interacting protein 1 (GRIP1)), SRC-3 amplified in breast cancer 1 (AIB1) and ACTR, cyclic AMP binding protein (CBP), and steroid receptor RNA activator (SRA), corepressors nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone recpetors (SMRT), and secondary coactivators coactivator associated arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 1 (PRMT1). We note both ligand-independent as well estradiol- and 4-hydroxytamoxifen-dependent differences in ER-coregulator activity. In vitro ER-ERE binding assays using receptor interaction domains of these coregulators failed to recapitulate the cell-based results, substantiating the importance of the full-length proteins in regulating ER activity. These data demonstrated that the ERE sequence impacts estradiol- and 4-hydroxytamoxifen-occupied ERα and ERβ interaction with coregulators as measured by transcriptional activity in mammalian cells.

Original languageEnglish (US)
Pages (from-to)387-410
Number of pages24
JournalJournal of Molecular Endocrinology
Volume33
Issue number2
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Co-Repressor Proteins
Response Elements
Estrogen Receptors
Transcriptional Activation
Estrogens
Nuclear Receptor Coactivator 2
Estradiol
Nuclear Receptor Coactivator 1
Protein-Arginine N-Methyltransferases
Estradiol Congeners
Ligands
CHO Cells
Retinoids
Thyroid Hormones
Cyclic AMP
Genes
Carrier Proteins
Breast Neoplasms

ASJC Scopus subject areas

  • Endocrinology

Cite this

Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors. / Klinge, Carolyn M.; Jernigan, Sarah; Mattingly, K. A.; Risinger, K. E.; Zhang, J.

In: Journal of Molecular Endocrinology, Vol. 33, No. 2, 10.2004, p. 387-410.

Research output: Contribution to journalArticle

Klinge, Carolyn M. ; Jernigan, Sarah ; Mattingly, K. A. ; Risinger, K. E. ; Zhang, J. / Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors. In: Journal of Molecular Endocrinology. 2004 ; Vol. 33, No. 2. pp. 387-410.
@article{2eb0754dd4704bc19c4e7173df509bae,
title = "Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors",
abstract = "One mechanism by which ligand-activated estrogen receptors α and β (ERα and ERβ) stimulate gene transcription is through direct ER interaction with specific DNA sequences, estrogen response elements (EREs). ERE-bound ER recruits coactivators that stimulate gene transcription. Binding of ER to natural and synthetic EREs with different nucleotide sequences alters ER binding affinity, conformation, and transcriptional activity, indicating that the ERE sequence is an allosteric effector of ER action. Here we tested the hypothesis that alterations in ER conformation induced by binding to different ERE sequences modulates ER interaction with coactivators and corepressors. CHO-K1 cells transfected with ERα or ERβ show ERE sequence-dependent differences in the functional interaction of ERα and ERβ with coactivators steroid receptor coativator 1 (SRC-1), SRC-2 (glucocorticoid receptor interacting protein 1 (GRIP1)), SRC-3 amplified in breast cancer 1 (AIB1) and ACTR, cyclic AMP binding protein (CBP), and steroid receptor RNA activator (SRA), corepressors nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone recpetors (SMRT), and secondary coactivators coactivator associated arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 1 (PRMT1). We note both ligand-independent as well estradiol- and 4-hydroxytamoxifen-dependent differences in ER-coregulator activity. In vitro ER-ERE binding assays using receptor interaction domains of these coregulators failed to recapitulate the cell-based results, substantiating the importance of the full-length proteins in regulating ER activity. These data demonstrated that the ERE sequence impacts estradiol- and 4-hydroxytamoxifen-occupied ERα and ERβ interaction with coregulators as measured by transcriptional activity in mammalian cells.",
author = "Klinge, {Carolyn M.} and Sarah Jernigan and Mattingly, {K. A.} and Risinger, {K. E.} and J. Zhang",
year = "2004",
month = "10",
doi = "10.1677/jme.1.01541",
language = "English (US)",
volume = "33",
pages = "387--410",
journal = "Journal of Molecular Endocrinology",
issn = "0952-5041",
publisher = "Society for Endocrinology",
number = "2",

}

TY - JOUR

T1 - Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors

AU - Klinge, Carolyn M.

AU - Jernigan, Sarah

AU - Mattingly, K. A.

AU - Risinger, K. E.

AU - Zhang, J.

PY - 2004/10

Y1 - 2004/10

N2 - One mechanism by which ligand-activated estrogen receptors α and β (ERα and ERβ) stimulate gene transcription is through direct ER interaction with specific DNA sequences, estrogen response elements (EREs). ERE-bound ER recruits coactivators that stimulate gene transcription. Binding of ER to natural and synthetic EREs with different nucleotide sequences alters ER binding affinity, conformation, and transcriptional activity, indicating that the ERE sequence is an allosteric effector of ER action. Here we tested the hypothesis that alterations in ER conformation induced by binding to different ERE sequences modulates ER interaction with coactivators and corepressors. CHO-K1 cells transfected with ERα or ERβ show ERE sequence-dependent differences in the functional interaction of ERα and ERβ with coactivators steroid receptor coativator 1 (SRC-1), SRC-2 (glucocorticoid receptor interacting protein 1 (GRIP1)), SRC-3 amplified in breast cancer 1 (AIB1) and ACTR, cyclic AMP binding protein (CBP), and steroid receptor RNA activator (SRA), corepressors nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone recpetors (SMRT), and secondary coactivators coactivator associated arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 1 (PRMT1). We note both ligand-independent as well estradiol- and 4-hydroxytamoxifen-dependent differences in ER-coregulator activity. In vitro ER-ERE binding assays using receptor interaction domains of these coregulators failed to recapitulate the cell-based results, substantiating the importance of the full-length proteins in regulating ER activity. These data demonstrated that the ERE sequence impacts estradiol- and 4-hydroxytamoxifen-occupied ERα and ERβ interaction with coregulators as measured by transcriptional activity in mammalian cells.

AB - One mechanism by which ligand-activated estrogen receptors α and β (ERα and ERβ) stimulate gene transcription is through direct ER interaction with specific DNA sequences, estrogen response elements (EREs). ERE-bound ER recruits coactivators that stimulate gene transcription. Binding of ER to natural and synthetic EREs with different nucleotide sequences alters ER binding affinity, conformation, and transcriptional activity, indicating that the ERE sequence is an allosteric effector of ER action. Here we tested the hypothesis that alterations in ER conformation induced by binding to different ERE sequences modulates ER interaction with coactivators and corepressors. CHO-K1 cells transfected with ERα or ERβ show ERE sequence-dependent differences in the functional interaction of ERα and ERβ with coactivators steroid receptor coativator 1 (SRC-1), SRC-2 (glucocorticoid receptor interacting protein 1 (GRIP1)), SRC-3 amplified in breast cancer 1 (AIB1) and ACTR, cyclic AMP binding protein (CBP), and steroid receptor RNA activator (SRA), corepressors nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone recpetors (SMRT), and secondary coactivators coactivator associated arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 1 (PRMT1). We note both ligand-independent as well estradiol- and 4-hydroxytamoxifen-dependent differences in ER-coregulator activity. In vitro ER-ERE binding assays using receptor interaction domains of these coregulators failed to recapitulate the cell-based results, substantiating the importance of the full-length proteins in regulating ER activity. These data demonstrated that the ERE sequence impacts estradiol- and 4-hydroxytamoxifen-occupied ERα and ERβ interaction with coregulators as measured by transcriptional activity in mammalian cells.

UR - http://www.scopus.com/inward/record.url?scp=7244247363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7244247363&partnerID=8YFLogxK

U2 - 10.1677/jme.1.01541

DO - 10.1677/jme.1.01541

M3 - Article

C2 - 15525597

AN - SCOPUS:7244247363

VL - 33

SP - 387

EP - 410

JO - Journal of Molecular Endocrinology

JF - Journal of Molecular Endocrinology

SN - 0952-5041

IS - 2

ER -