Coregulatory Proteins in Nuclear Hormone Receptor Action

Edwards, Dean P.

doi:10.1016/s0083-6729(08)60936-x

Cited by 51 publications

(25 citation statements)

References 217 publications

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“…These efforts have lead to the identification and characterization of several distinct multiprotein complexes which directly interact with agonist-bound nuclear receptors (9,16,28,45,46). The SRC-1 family of nuclear receptor coactivators appear to play a critical role in mediating the association of one of these complexes to nuclear receptors.…”

Section: Discussionmentioning

confidence: 99%

BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

DiRenzo

Shang

Phelan

et al. 2000

Molecular and Cellular Biology

205

142

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Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent. We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER-BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin.Precise regulation of gene expression underlies the ability of a cell to control growth and to acquire and execute physiologic functions. Broad arrays of cellular signals are transduced to the nucleus, where many act on transcription factors. These diverse regulatory signals must be integrated into smaller subsets that can be transmitted to targets that modulate the basal transcription machinery. One such target is chromatin, and there exists abundant evidence that the structure and chemical composition of chromatin directly affect gene expression (35). The primary structural components of chromatin, the histones, are enzymatically acetylated, and this acetylation results in a reduced affinity for DNA and enhanced binding affinity for certain transcriptional coregulators (7). Chromatin structure is also altered via the ATP-dependent disruption of nucleosomes by large multiprotein chromatin remodeling complexes (3). One such complex, the Swi/Snf complex, is well conserved through evolution and functions as a global regulator of transcription (37). These and other mechanisms account for the link between the chemical and structural modification of chromatin and transcriptional activation by members of the nuclear receptor superfamily.The nuclear receptor superfamily ...

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Section: Discussionmentioning

confidence: 99%

BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

DiRenzo

Shang

Phelan

et al. 2000

Molecular and Cellular Biology

205

142

View full text Add to dashboard Cite

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“…In addition, more than 100 other DNAbinding proteins have been identified that contain an HMG box, including the testis-determining factor SRY and the LEF1 transcription factor (Baxevanis and Landsman, 1995). The HMGA subfamily has been shown to modulate the activity of estrogen and progesterone receptors (Verrier et al, 1997;Boonyaratanakornkit et al, 1998;Romine et al, 1998;Zhang et al, 1999), thus defining HMG proteins as members of the nuclear hormone coregulatory protein family (Edwards, 1999;Melvin and Edwards, 1999).…”

Section: The Road Less Traveled: Finding the Convergence In Molecularmentioning

confidence: 99%

Uterine leiomyoma in the Eker rat: A unique model for important diseases of women

Walker

Hunter

Everitt

2003

Genes Chromosomes & Cancer

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Eker rats carry a defect in the Tsc-2 tumor suppressor gene and female Eker rats develop uterine leiomyoma with a high frequency. The presentation, response to hormones and molecular alterations in these mesenchymal smooth muscle tumors, closely resembles their cognate human disease. Female rats and tumor-derived cell lines from Eker rat leiomyomas (ELT lines) have been developed as an in vivo/in vitro model system for preclinical studies to identify novel therapeutic agents for this disease and for studying disease pathogenesis. In addition to serving as a model for uterine leiomyoma, Eker rats have proven valuable for studying lymphangioleiomyomatosis, a related proliferative smooth muscle disease of women.

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“…Transcriptional regulation by nuclear hormone receptors involves participation of basal transcription factors, including TATA-binding protein and TFIIB, and other cofactors, known as nuclear transcriptional coactivators or corepressors, that form bridges between nuclear receptors and the basal transcription machinery (Polak 1997, Edwards 1999, Robyr et al 2000. Many nuclear hormone receptors possess bimodal transcriptional properties and are capable of either repressing or activating target gene transcription, depending on the status of the ligand, the promoter and the nature of the host cell (Polak 1997, Gottlicher et al 1998, Gay et al 2002.…”

Section: Introductionmentioning

confidence: 99%

Functional interference between estrogen-related receptor alpha and peroxisome proliferator-activated receptor alpha/9-cis-retinoic acid receptor alpha heterodimer complex in the nuclear receptor response element-1 of the medium chain acyl-coenzyme A dehydrogenase gene

Maehara¹,

Hida²,

Abe³

et al. 2003

Journal of Molecular Endocrinology

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We undertook a study of molecular interference of nuclear orphan receptors. Nuclear receptor response element-1 (NRRE-1) from the human medium-chain acyl coenzyme A dehydrogenase (MCAD) gene promoter was shown to contain three hexamer elements (site 1 through 3) that are known to interact with a number of nuclear receptors including chicken ovalbumin upstream promoter transcription factor (COUP-TF) and estrogen-related receptor alpha (ERRα). We demonstrated that the peroxisome proliferator-activated receptor alpha/9-cis-retinoic acid receptor alpha (PPARα/RXRα) heterodimer complex can also bind to the two hexamer repeat sequences (between site 1 and site 3) arranged as an everted imperfect repeat separated by 14 bp (ER14). Mutations of the putative core elements have shown that these three sites are differentially involved in ERRα and PPARα/RXRα binding. Homodimer of ERRα was shown to interact between site 1 and site 3 (ER14). To date, no nuclear receptor is known to bind to response elements over such long intervals. Interestingly, site 1 was shown to be essential for ERRα binding while site 3 supports its binding only in the presence of site 1. Furthermore, it was shown that the binding profile of ERRα and PPARα/RXRα are competitive rather than making a high order complex within NRRE-1. At the cellular level, transcriptional activation driven by the PPARα/RXRα complex was counteracted by the expression of ERRα in HeLa cells. These results suggest that ERRα and PPARα/RXRα could interfere with each other's function through binding to similar DNA elements, thereby finetuning the transcriptional outcome of the target gene. Our findings suggest a mechanism whereby multiple nuclear receptors can activate or repress DNA binding or transcription via a single pleiotropic regulatory element.

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Coregulatory Proteins in Nuclear Hormone Receptor Action

Cited by 51 publications

References 217 publications

BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

Uterine leiomyoma in the Eker rat: A unique model for important diseases of women

Functional interference between estrogen-related receptor alpha and peroxisome proliferator-activated receptor alpha/9-cis-retinoic acid receptor alpha heterodimer complex in the nuclear receptor response element-1 of the medium chain acyl-coenzyme A dehydrogenase gene

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