TY - CHAP
T1 - Transcriptional activation of genes by 17β-estradiol through estrogen receptor-Sp1 interactions
AU - Safe, Stephen
N1 - Funding Information:
The financial assistance of the National Institutes of Health (CA76636 and ES09253) and the Texas Agricultural Experiment Station is gratefully acknowledged. The assistance of Ismael Samudio is also appreciated. S. Safe is a Sid Kyle Professor of Toxicology.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - Estrogen receptor-α (ERα) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. The classic mechanism of (ERα) action is associated with estrogen-induced formation of a nuclear (ERα) homodimer, binding to 5′-regulatory estrogen response elements (EREs) in target gene promoters, interaction with other nuclear proteins, and general transcription factors to activate gene expression. (ERα) also interacts with Sp1 protein to transactivate genes through binding Sp1(N)xERE or Sp1(N)xERE half-site ( 1 2) motifs where both (ERα) and Sp1 bind DNA elements. Activation through Sp1 (N)xERE 1 2 requires interactions of both proteins with their cognate DNA elements as well as additional nuclear factors to form a functional ERα/Sp1-DNA complex. Recent studies also show that (ERα) and Sp1 physically interact and (ERα) preferentially binds to the C-terminal DNA-binding domain of Sp1 protein. Moreover, ERα/Sp1 can activate transcription from a consensus GC-rich Sp1 binding site in transient transfection studies in MCF-7 human breast cancer cells, and this response is also observed with ERα variants that do not contain the DNA-binding domain. Several genes that are induced by estrogens in MCF-7 cells are activated through one or more GC-rich sites in their regulatory regions and these include the cathepsin D, E2F1, bcl-2, c-fos, adenosine deaminase, insulinlike growth factor binding protein 4, and retinoic acid receptor α1 genes. ERα/Sp1 and ERβ/Sp1 action is dependent on ligand structure and cell context and ERβ/Sp1 is primarily associated with decreased ligand-dependent gene expression. ERα/Sp1, like ERα/AP1, represents a pathway for hormone activation of genes in which the receptor does not bind DNA, and results of ongoing studies suggest that ERα/Sp1 plays an important role in transcriptional activation of multiple growth regulatory genes in breast cancer cells.
AB - Estrogen receptor-α (ERα) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. The classic mechanism of (ERα) action is associated with estrogen-induced formation of a nuclear (ERα) homodimer, binding to 5′-regulatory estrogen response elements (EREs) in target gene promoters, interaction with other nuclear proteins, and general transcription factors to activate gene expression. (ERα) also interacts with Sp1 protein to transactivate genes through binding Sp1(N)xERE or Sp1(N)xERE half-site ( 1 2) motifs where both (ERα) and Sp1 bind DNA elements. Activation through Sp1 (N)xERE 1 2 requires interactions of both proteins with their cognate DNA elements as well as additional nuclear factors to form a functional ERα/Sp1-DNA complex. Recent studies also show that (ERα) and Sp1 physically interact and (ERα) preferentially binds to the C-terminal DNA-binding domain of Sp1 protein. Moreover, ERα/Sp1 can activate transcription from a consensus GC-rich Sp1 binding site in transient transfection studies in MCF-7 human breast cancer cells, and this response is also observed with ERα variants that do not contain the DNA-binding domain. Several genes that are induced by estrogens in MCF-7 cells are activated through one or more GC-rich sites in their regulatory regions and these include the cathepsin D, E2F1, bcl-2, c-fos, adenosine deaminase, insulinlike growth factor binding protein 4, and retinoic acid receptor α1 genes. ERα/Sp1 and ERβ/Sp1 action is dependent on ligand structure and cell context and ERβ/Sp1 is primarily associated with decreased ligand-dependent gene expression. ERα/Sp1, like ERα/AP1, represents a pathway for hormone activation of genes in which the receptor does not bind DNA, and results of ongoing studies suggest that ERα/Sp1 plays an important role in transcriptional activation of multiple growth regulatory genes in breast cancer cells.
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U2 - 10.1016/s0083-6729(01)62006-5
DO - 10.1016/s0083-6729(01)62006-5
M3 - Chapter
C2 - 11345900
AN - SCOPUS:0035228654
SN - 0127098623
SN - 9780127098623
T3 - Vitamins and Hormones
SP - 231
EP - 252
BT - Vitamins and Hormones
PB - Academic Press
ER -