Rush hour at the promoter: How the ubiquitin-proteasome pathway polices the traffic flow of nuclear receptor-dependent transcription

Dennis, Andrew P.; O’Malley, Bert W.

doi:10.1016/j.jsbmb.2004.12.015

Cited by 61 publications

(55 citation statements)

References 147 publications

(155 reference statements)

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“…enhancement of gene expression ͉ nuclear architecture ͉ chromosomal movement ͉ interchromosomal interactions ͉ SC35 domains T he molecular mechanism used by nuclear receptors to mediate coactivator/corepressor exchanges in gene activation has been well elucidated (1,2). However, recent genome-wide analyses of DNA binding sites for transcription factors, including estrogen receptor (ER␣), revealed numerous intergenic sites, only a few of which have clearly been established to function as enhancers in vivo (3)(4)(5), raising intriguing questions about whether and how some of these remote binding sites might communicate with their putative target genes via long-distance intrachromosomal and (potentially) interchromosomal interactions.…”

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confidence: 99%

Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules

Kwon

Núñez

et al. 2008

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

251

253

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Fig. 2. Rapid induction of interchromosomal interactions by nuclear hormone signaling. (A) 3D-FISH confirmation of E 2 -induced (60 min) TFF1:GREB1 interchromosomal interactions in HMECs with the distribution of loci distances measured (box plot with scatter plot) and quantification of colocalization (bar graph) before and after E 2 treatment. Cells exhibiting mono-or biallelic interactions were combined for comparison with cells showing no colocalization; statistical significance in the bar graph was determined by χ 2 test (**, P < 0.001). (B) 2D FISH confirmation of the interchromosomal interactions in HMEC cells by combining chromosome paint (aqua) and specific DNA probes (green and red). (Upper) Illustrates two examples of mock-treated cells. (Lower) Shows the biallelic interactions/ nuclear reorganization after E 2 treatment for 60 min, exhibiting kissing events between chromosome 21 and chromosome 2. (C) Similar analysis on HMECs, but in this case using 3D FISH to paint chromosome 2 (red) and chromosome 21 (green), showing E 2 -induced chromosome 2-chromosome 21 interaction. Both assays revealed neither chromosome 21-chromosome 21 nor chromosome 2-chromosome 2 interactions in response to E 2. (D) Temporal kinetics of GREB1:TFF1 interactions by 3D FISH in HMECs (**, P < 0.001 by χ 2 ). (E-G) Nuclear microinjection of siRNA against ERα, CBP/p300, or SRC1/pCIP prevented E 2 -induced interchromosomal interactions, counting both mono-and biallelic interactions (**, P < 0.001 by χ 2 ). The injection of siER and siDLC1 were done in the same experiment, sharing the same control group. (H) Nuclear microinjection of siRNA against LSD1, which was shown to be required for estrogen-induced gene expression (22), did not block E 2 -induced interchromosomal interactions. The injection of siLSD1 and SRC1/pCIP were done in a single experiment, sharing the same control group.

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confidence: 99%

Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules

Kwon

Núñez

et al. 2008

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

251

253

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“…Gene activation by ligand-activated nuclear receptors involves remodeling of promoter composition (53,54). This process requires a change in the covalent modification status of chromatin-associated proteins.…”

Section: Discussionmentioning

confidence: 99%

“…This process requires a change in the covalent modification status of chromatin-associated proteins. Ubiquitination of transcription factors and their 26 S proteasomal degradation has emerged as an important mechanism controlling promoter composition (53)(54)(55). Inhibitors of the 26 S proteasome significantly affect gene activation.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Rat Hepatic L-Pyruvate Kinase Promoter Composition and Activity by Glucose, n-3 Polyunsaturated Fatty Acids, and Peroxisome Proliferator-activated Receptor-α Agonist

Christian

Jump

2006

Journal of Biological Chemistry

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Carbohydrate regulatory element-binding protein (ChREBP), MAX-like factor X (MLX), and hepatic nuclear factor-4␣ (HNF-4␣) are key transcription factors involved in the glucose-mediated induction of hepatic L-type pyruvate kinase (L-PK) gene transcription. n-3 polyunsaturated fatty acids (PUFA) and WY14643 (peroxisome proliferatoractivated receptor ␣ (PPAR␣) agonist) interfere with glucose-stimulated L-PK gene transcription in vivo and in rat primary hepatocytes. Feeding rats a diet containing n-3 PUFA or WY14643 suppressed hepatic mRNA L-PK but did not suppress hepatic ChREBP or HNF-4␣ nuclear abundance. Hepatic MLX nuclear abundance, however, was suppressed by n-3 PUFA but not WY14643. In rat primary hepatocytes, glucose-stimulated accumulation of mRNA LPK and L-PK promoter activity correlated with increased ChREBP nuclear abundance. This treatment also increased L-PK promoter occupancy by RNA polymerase II (RNA pol II), acetylated histone H3 (Ac-H3), and acetylated histone H4 (Ac-H4) but did not significantly impact L-PK promoter occupancy by ChREBP or HNF-4␣. Inhibition of L-PK promoter activity by n-3 PUFA correlated with suppressed RNA pol II, Ac-H3, and Ac-H4 occupancy on the L-PK promoter. Although n-3 PUFA transiently suppressed ChREBP and MLX nuclear abundance, this treatment did not impact ChREBP-LPK promoter interaction. HNF4␣-LPK promoter interaction was transiently suppressed by n-3 PUFA. Inhibition of L-PK promoter activity by WY14643 correlated with a transient decline in ChREBP nuclear abundance and decreased Ac-H4 interaction with the L-PK promoter. WY14643, however, had no impact on MLX nuclear abundance or HNF4␣-LPK promoter interaction. Although overexpressed ChREBP or HNF-4␣ did not relieve n-3 PUFA suppression of L-PK gene expression, overexpressed MLX fully abrogated n-3 PUFA suppression of L-PK promoter activity and mRNA L-PK abundance. Overexpressed ChREBP, but not MLX, relieved the WY14643 inhibition of L-PK. In conclusion, n-3 PUFA and WY14643/PPAR␣ target different transcription factors to control L-PK gene transcription. MLX, the heterodimer partner for ChREBP, has emerged as a novel target for n-3 PUFA regulation.The glycolytic enzyme, liver-type pyruvate kinase (L-PK), 2 plays a key role in hepatic glucose and lipid metabolism (1). Phosphorylation and allosteric factors acutely regulate L-PK enzyme activity, whereas hormones and nutrients chronically control the abundance of L-PK protein by regulating L-PK gene transcription. Excess glucose consumption induces glycolysis, L-PK activity, de novo lipogenesis, and lipid storage, whereas n-3 polyunsaturated fatty acids (n-3 PUFA) inhibit these metabolic events (2, 3). L-PK gene transcription is induced by insulin-stimulated glucose metabolism (4) and inhibited by n-3 PUFA and activators of PPAR␣ (WY14643), protein kinase A, and AMP kinase (AMPK) (5-8).Key cis-regulatory elements controlling L-PK gene transcription are located between Ϫ197 and Ϫ125 bp upstream of the transcription start site (Fig. 1). Two basic helix-loop-helix transcri...

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“…A large body of literature shows that components of the ubiquitin/proteasome system play an important role at the promoter of nuclear receptors-target genes by regulating chromatin structure and the turnover of receptors and coregulators, and by serving as bridging factors [67,68]. Recent studies showed that proteasome activity is also important for modulating AR transcriptional activation [69].…”

Section: Involvement Of Ubiquitin and The 26s Proteasome In The Formamentioning

confidence: 99%

Degradation and beyond: Control of androgen receptor activity by the proteasome system

Jaworski

2006

Cellular and Molecular Biology Letters

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The androgen receptor (AR) is a transcription factor belonging to the family of nuclear receptors which mediates the action of androgens in the development of urogenital structures. AR expression is regulated post-translationally by the ubiquitin/proteasome system. This regulation involves more complex mechanisms than typical degradation. The ubiquitin/proteasome system may regulate AR via mechanisms that do not engage in receptor turnover. Given the critical role of AR in sexual development, this complex regulation is especially important. Deregulation of AR signalling may be a causal factor in prostate cancer development. AR is the main target in prostate cancer therapies. Due to the critical role of the ubiquitin/proteasome system in AR regulation, current research suggests that targeting AR degradation is a promising approach.

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Rush hour at the promoter: How the ubiquitin-proteasome pathway polices the traffic flow of nuclear receptor-dependent transcription

Cited by 61 publications

References 147 publications

Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules

Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules

Regulation of Rat Hepatic L-Pyruvate Kinase Promoter Composition and Activity by Glucose, n-3 Polyunsaturated Fatty Acids, and Peroxisome Proliferator-activated Receptor-α Agonist

Degradation and beyond: Control of androgen receptor activity by the proteasome system

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