Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription

Dilworth, F. Jeffrey; Chambon, Pierre

doi:10.1038/sj.onc.1204329

Cited by 242 publications

(178 citation statements)

References 83 publications

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“…Then, in a second wave of coactivator recruitment, pCAF and the p300-related protein CBP arrived on the ERbound promoter, leading to productive transcription initiation. Thus, it seems that sequential coactivator recruitment to promoters is a common mechanism by which several different families of activators establish a transcriptionally competent promoter (31).…”

Section: Discussionmentioning

confidence: 99%

In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

Dilworth

Seaver

Fishburn

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The transcriptional coactivators p300 and pCAF are necessary for the myogenic factor MyoD to initiate the expression of skeletal muscle genes. In addition to mediating histone acetylation, both of these factors can acetylate MyoD; however, the complexity of cellular systems used to study MyoD has impeded delineation of the specific roles of these two acetyltransferases. Therefore, we established a MyoD-dependent in vitro transcription system that permits us to determine the roles of p300 and pCAF during MyoD-dependent transcriptional activation. Consistent with results from cellular systems, we demonstrate that maximal levels of transactivation in vitro require both p300 and pCAF, as well as the cofactor acetyl CoA. Dissection of the steps leading to transcription initiation revealed that the activities of p300 and pCAF are not redundant. During the initial stages of transactivation, p300 acetylates histone H3 and H4 within the promoter region and then recruits pCAF to MyoD. Once tethered to the promoter, pCAF acetylates MyoD to facilitate the transactivation process. Thus, we have established that pCAF and p300 carry out sequential and functionally distinct events on a promoter leading to transcriptional activation. Further dissection of this in vitro transcription system should be highly useful toward elucidating the mechanism by which coactivators facilitate differential gene expression by MyoD.

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Section: Discussionmentioning

confidence: 99%

In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

Dilworth

Seaver

Fishburn

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…RARs can heterodimerize with the rexinoid receptors, RXRs, and upon RA binding, they can recruit coactivator protein complexes and chromatin remodeling complexes. These complexes can impose critical histone modifications, such as acetylation of specific lysine residues, and lead to conformational changes of the chromatin, ultimately enabling transcriptional activation by the RNA Polymerase II (Pol II) (Dilworth and Chambon, 2001).…”

Section: Introductionmentioning

confidence: 99%

RAR-mediated epigenetic control of the cytochrome P450 Cyp26a1 in embryocarcinoma cells

et al. 2005

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“…The coactivator comprises a protein complex that includes factors possessing histone acetylase or chromatin remodeling activity, which will loosen the chromatin structure and promote the recruitment of the transcription apparatus [13] . When the receptor is occupied with an antagonist or free from ligands, it is associated with a transcriptional corepressor that represses transcription [14] .…”

Section: Steroid Hormone Receptorsmentioning

confidence: 99%

Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology

2014

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Estrogens are important endocrine hormones that control physiological functions in reproductive organs, and play a pivotal role in the generation and progression of breast cancer. Therapeutic drugs including anti-estrogen and aromatase inhibitors are used to treat patients with breast cancer. The estrogen receptors, ERα and ERβ, function as hormone-dependent transcription factors that directly regulate the expression of their target genes. Therefore, a better understanding of the function and regulation of estrogen-responsive genes provides insight into the gene regulation network associated with breast cancer. Recent technological developments in highthroughput sequencing have enabled the genome-wide identification of estrogen-responsive genes. Further elucidating the estrogen gene cascade is critical for advancements in the diagnosis and treatment of breast cancer.

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Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription

Cited by 242 publications

References 83 publications

In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

RAR-mediated epigenetic control of the cytochrome P450 Cyp26a1 in embryocarcinoma cells

Identification of estrogen-responsive genes based on the DNA binding properties of estrogen receptors using high-throughput sequencing technology

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