Requirement of cofactors for RXR/RAR-mediated transcriptional activation in vitro

Valcárcel, Rafael; Meyer, Markus; Meisterernst, Michael; Stunnenberg, Hendrik G.

doi:10.1016/s0167-4781(96)00234-5

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…This in turn provided us with a direct, cell-free assay system to test the functionality of the DRIPs. A similar strategy has been used to fractionate crude nuclear extracts that are apparently distinct from known general transcription factors but are nevertheless required for retinoic acid-dependent transcription in vitro (Valcarcel et al 1997). Here, the addition of the VDR-DRIP complex to the transcription extract enhanced VDR-RXR transcription from a VDRE template to a greater extent than the addition of exogenous VDR and RXR alone, implying that one or all of the DRIPs are limiting in the extract.…”

Section: (B) Multiple Tissue Northern Blot Of Drip100 Two Microgramentioning

confidence: 99%

A novel protein complex that interacts with the vitamin D₃ receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system

Rachez

Suldan²,

Ward³

et al. 1998

Genes Dev.

357

246

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Steroid, retinoid, vitamin D 3 , and thyroid hormones signal through ligand-dependent transcription factors that collectively comprise a superfamily of intracellular, soluble receptors (hereafter collectively called nuclear receptors) that reside in the nucleus or translocate there in response to hormonal signals. As the largest known family of eukaryotic transcriptional regulators, nuclear receptors are implicated via the target genes they modulate in the control of cell growth and differentiation, homeostasis, development, and several physiological processes (for review, see Freedman 1997 and references therein). Moreover, because they are regulated tightly by small lipophilic molecules, they are extremely attractive as pharmacologic targets.Nuclear receptors all share a common organization in functional domains and extensive homologies in structure. A DNA-binding domain allows the receptors to bind as homodimers, or heterodimers with a common partner, retinoid X receptor (RXR), to specific DNA response elements typically composed of two hexameric half-sites organized as direct or inverted repeats. The carboxy-terminal half of the prototype nuclear receptor includes a ligand-binding domain (LBD) with a superimposed dimerization surface, and a ligand-dependent transcriptional activation function called AF-2, located at the extreme carboxyl terminus of the receptor (Danielian et al. 1992;Barettino et al. 1994;Durand et al. 1994). Crystallographic analyses have revealed that binding of a specific ligand, all-trans retinoic acid (ATRA), to retinoic acid receptor ␥ (RAR␥) induces a conformational change in its structure that modifies the orientation of the AF-2 core motif, contained within the last of 12 ␣-helices that

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Section: (B) Multiple Tissue Northern Blot Of Drip100 Two Microgramentioning

confidence: 99%

A novel protein complex that interacts with the vitamin D₃ receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system

Rachez

Suldan²,

Ward³

et al. 1998

Genes Dev.

357

246

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“…This gene is under the control of a promoter that contains a canonical (proximal) retinoic acid response element (RARE) composed of a DR‐5 element. It also contains a cAMP‐responsive element and an auxiliary (distal) RARE (Sanguedolce et al ., 1997; Valcarcel et al ., 1997). Previous studies indicated that the mRARβ2 promoter activation is regulated by chromatin.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of histone H3 is functionally linked to retinoic acid receptor β promoter activation

2002

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Ligand-dependent transcriptional activation of retinoic acid receptors (RARs) is a multistep process culminating in the formation of a multimeric co-activator complex on regulated promoters. Several co-activator complexes harbor an acetyl transferase activity, which is required for retinoid-induced transcription of reporter genes. Using murine P19 embryonal carcinoma cells, we examined the relationship between histone post-translational modifications and activation of the endogenous RARβ2 promoter, which is under the control of a canonical retinoic acid response element and rapidly induced upon retinoid treatment. While histones H3 and H4 were constitutively acetylated at this promoter, retinoid agonists induced a rapid phosphorylation at Ser10 of histone H3. A retinoid antagonist, whose activity was independent of co-repressor binding to RAR, could oppose this agonist-induced H3 phosphorylation. Since such post-translational modifications were not observed at several other promoters, we conclude that histone H3 phosphorylation may be a molecular signature of the activated, retinoid-controlled mRARβ2 gene promoter.

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“…This gene is under the control of a promoter that contains a canonical (proximal) RARE composed of a DR-5 element. It also contains a cyclic AMP (cAMP) response element and an auxiliary (distal) RARE (58,62) (Fig. 1A).…”

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Chromosomal Integration of Retinoic Acid Response Elements Prevents Cooperative Transcriptional Activation by Retinoic Acid Receptor and Retinoid X Receptor

Lefebvre

Brand

Lefèbvre

et al. 2002

Molecular and Cellular Biology

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All-trans-retinoic acid receptors (RAR) and 9-cis-retinoic acid receptors (RXR) are nuclear receptors known to cooperatively activate transcription from retinoid-regulated promoters. By comparing the transactivating properties of RAR and RXR in P19 cells using either plasmid or chromosomal reporter genes containing the mRAR␤2 gene promoter, we found contrasting patterns of transcriptional regulation in each setting. Cooperativity between RXR and RAR occurred at all times with transiently introduced promoters, but was restricted to a very early stage (<3 h) for chromosomal promoters. This time-dependent loss of cooperativity was specific for chromosomal templates containing two copies of a retinoid-responsive element (RARE) and was not influenced by the spacing between the two RAREs. This loss of cooperativity suggested a delayed acquisition of RAR full transcriptional competence because (i) cooperativity was maintained at RAR ligand subsaturating concentrations, (ii) overexpression of SRC-1 led to loss of cooperativity and even to strong repression of chromosomal templates activity, and (iii) loss of cooperativity was observed when additional cis-acting response elements were activated. Surprisingly, histone deacetylase inhibitors counteracted this loss of cooperativity by repressing partially RAR-mediated activation of chromosomal promoters. Loss of cooperativity was not correlated to local histone hyperacetylation or to alteration of constitutive RNA polymerase II (RNAP) loading at the promoter region. Unexpectedly, RNAP binding to transcribed regions was correlated to the RAR activation state as well as to acetylation levels of histones H3 and H4, suggesting that RAR acts at the mRAR␤ promoter by triggering the switch from an RNA elongation-incompetent RNAP form towards an RNA elongation-competent RNAP.

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Requirement of cofactors for RXR/RAR-mediated transcriptional activation in vitro

Cited by 5 publications

References 38 publications

A novel protein complex that interacts with the vitamin D₃ receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system

A novel protein complex that interacts with the vitamin D₃ receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system

Phosphorylation of histone H3 is functionally linked to retinoic acid receptor β promoter activation

Chromosomal Integration of Retinoic Acid Response Elements Prevents Cooperative Transcriptional Activation by Retinoic Acid Receptor and Retinoid X Receptor

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Requirement of cofactors for RXR/RAR-mediated transcriptional activation in vitro

Cited by 5 publications

References 38 publications

A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system

A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system

Phosphorylation of histone H3 is functionally linked to retinoic acid receptor β promoter activation

Chromosomal Integration of Retinoic Acid Response Elements Prevents Cooperative Transcriptional Activation by Retinoic Acid Receptor and Retinoid X Receptor

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A novel protein complex that interacts with the vitamin D₃ receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system

A novel protein complex that interacts with the vitamin D₃ receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system