Activated Signal Transduction Kinases Frequently Occupy Target Genes

Pokholok, Dmitry; Zeitlinger, Julia; Hannett, Nancy M.; Reynolds, David; Young, Richard A.

doi:10.1126/science.1127677

Cited by 232 publications

(248 citation statements)

References 26 publications

(2 reference statements)

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“…Moreover, the fact that both ERK1/2 and PKB inhibition seem to reverse the effects of ISO stimulation on these identified genes would seem to indicate that both pathways play a role in the regulation of gene expression by nuclear βARs. This may be through MAPK or PKB modulation of the signalling proteins themselves, modulation of the transcriptional machinery or via alterations in the occupancy of chromatin sites by ERK and other protein kinases [43,44]. Further, given the already identified role of MAPKs in regulating mRNA stability [45], further experiments need to be conducted to determine if the regulation that we see is actually due to a changes in the level of de novo mRNA synthesis or reduced mRNA stability.…”

Section: Discussionmentioning

confidence: 93%

Nuclear β-adrenergic receptors modulate gene expression in adult rat heart

Vaniotis

Duca

Trieu

et al. 2011

Cellular Signalling

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Both β 1 -and β 3 -adrenergic receptors (β 1 ARs and β 3 ARs) are present on nuclear membranes in adult ventricular myocytes. These nuclear-localized receptors are functional with respect to ligand binding and effector activation. In isolated cardiac nuclei, the non-selective βAR agonist isoproterenol stimulated de novo RNA synthesis measured using assays of transcription initiation (Boivin et al., 2006 Cardiovasc Res. 71:69-78). In contrast, stimulation of endothelin receptors, another G protein-coupled receptor (GPCR) that localizes to the nuclear membrane, resulted in decreased RNA synthesis. To investigate the signalling pathway(s) involved in GPCR-mediated regulation of RNA synthesis, nuclei were isolated from intact adult rat hearts and treated with receptor agonists in the presence or absence of inhibitors of different mitogen-activated protein kinase (MAPK) and PI3K/PKB pathways. Components of p38, JNK, and ERK1/2 MAP kinase cascades as well as PKB were detected in nuclear preparations. Inhibition of PKB with triciribine, in the presence of isoproterenol, converted the activation of the βAR from stimulatory to inhibitory with regards to RNA synthesis, while ERK1/2, JNK and p38 inhibition reduced both basal and isoproterenol-stimulated activity. Analysis by qPCR indicated an increase in the expression of 18 S rRNA following isoproterenol treatment and a decrease in NFκB mRNA. Further qPCR experiments revealed that isoproterenol treatment also reduced the expression of several other genes involved in the activation of NFκB, while ERK1/2 and PKB inhibition substantially * Corresponding authors. Hébert is to be contacted

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Section: Discussionmentioning

confidence: 93%

Nuclear β-adrenergic receptors modulate gene expression in adult rat heart

Vaniotis

Duca

Trieu

et al. 2011

Cellular Signalling

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“…WRKY factors can associate with MAP kinases in the nucleus, and MAP kinase cascades constitute key components of plant defense signaling. In yeast, the majority of terminal MAP kinases appear to be within the nucleus, associated with transcriptional complexes at target genes (Pokholok et al, 2006). Hence, one can expect that future studies will reveal additional nuclear functions of such WRKY-MAP kinase associations involving chromatin remodeling at target DNA sites.…”

Section: Resultsmentioning

confidence: 99%

The Role of WRKY Transcription Factors in Plant Immunity

2009

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“…More generally, the finding of tetramer splitting at specific genomic loci may have broader significance, because multiple assembly factors and histone chaperones mediate H3-H4 exchange in concert with other cellular processes such as DNA repair and DNA amplification. In the case of Pol II transcription, tetramer splitting may also depend on environmental conditions, and in this regard, stress-activated kinases (e.g., Hog1, Fus3, PKA) are recruited specifically to stress-activated coding regions (32,33). It is also conceivable that, in certain cell types or developmental stages, specific H3-H4 exchange processes might generate elevated levels of mixed tetramers at distinct parts of the genome.…”

Section: Relative Ip Efficiencymentioning

confidence: 99%

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

Katan-Khaykovich

Struhl

2011

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

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Nucleosome deposition occurs on newly synthesized DNA during DNA replication and on transcriptionally active genes via nucleosome-remodeling complexes recruited by activator proteins and elongating RNA polymerase II. It has been long believed that histone deposition involves stable H3-H4 tetramers, such that newly deposited nucleosomes do not contain H3 and H4 molecules with their associated histone modifications from preexisting nucleosomes. However, biochemical analyses and recent experiments in mammalian cells have raised the idea that preexisting H3-H4 tetramers might split into dimers, resulting in mixed nucleosomes composed of "old" and "new" histones. It is unknown to what extent different genomic loci might utilize such a mechanism and under which circumstances. Here, we address whether tetramer splitting occurs in a locus-specific manner by using sequential chromatin immunoprecipitation of mononucleosomes from yeast cells containing two differentially tagged versions of H3 that are expressed "old" and "new" histones. At many genomic loci, we observe little or no nucleosomal cooccupancy of old and new H3, indicating that tetramer splitting is generally infrequent. However, cooccupancy is detected at highly active genes, which have a high rate of histone exchange. Thus, DNA replication largely results in nucleosomes bearing exclusively old or new H3-H4, thereby precluding the acquisition of new histone modifications based on preexisting modifications within the same nucleosome. In contrast, tetramer splitting, dimer exchange, and nucleosomes with mixed H3-H4 tetramers occur at highly active genes, presumably linked to rapid histone exchange associated with robust transcription.T he packaging of eukaryotic DNA into chromatin influences many DNA-associated processes, including transcriptional regulation. Within the chromatin fiber, each basic nucleosome unit bears important chemical and structural information. The mechanisms by which nucleosomes are assembled on DNA during replication, transcription, DNA repair, etc., can thus impact not only the integrity of chromatin structure but also patterns of gene expression and epigenetic inheritance. The H3-H4 tetramer core of each nucleosome is the more stable component and contains most of the relatively persistent and functionally important histone methylation marks. Much attention has therefore been given to the questions of how the H3-H4 tetramers are formed and maintained on chromatin.Early studies attempted to distinguish between a conservative assembly model, by which old and new histones form separate tetramers on replicating DNA, and a semiconservative assembly mechanism, by which existing tetramers are split into H3-H4 dimers, followed by association of new H3-H4 dimers to complete each nucleosome core (1-3). In the semiconservative model, the resulting tetramers would bear a mixture of old and new histones, allowing transmission of epigenetic information within the basic nucleosome unit. Though mechanistically attractive, the mixed tetramer model receiv...

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Activated Signal Transduction Kinases Frequently Occupy Target Genes

Cited by 232 publications

References 26 publications

Nuclear β-adrenergic receptors modulate gene expression in adult rat heart

Nuclear β-adrenergic receptors modulate gene expression in adult rat heart

The Role of WRKY Transcription Factors in Plant Immunity

Splitting of H3–H4 tetramers at transcriptionally active genes undergoing dynamic histone exchange

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