Presetting of chromatin structure and transcription factor binding poise the human GADD45 gene for rapid transcriptional up-regulation

Graunke, Dawn M.; Fornace, Albert J.; Pieper, Russell O.

doi:10.1093/nar/27.19.3881

Cited by 25 publications

(25 citation statements)

References 20 publications

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“…Standard deviation of the mean are indicated by bars Oncogene N-oct3 mediated-induction of gadd45 following UVB K Lefort et al demonstrating that it does not take any part in the UVC-response of gadd45. These observations are consistent with other studies reporting the localization of DNase I hypersensitive sites in this same region of gadd45 promoter following ionizing radiation (Graunke et al, 1999) and camptothecin treatment (Xiao et al, 2000). In this context, EMSA performed on this 50 bp region of the gadd45 promoter led us to determine that the responsive elements that mediate gadd45 UVB-induction are the octamer ATGCAAAT since no DNA/protein complex was formed when these two octamer motives were mutated.…”

Section: Discussionsupporting

confidence: 93%

“…Most studies related to gadd45 expression in response to DNA damage have used genotoxic agents such as ionizing radiation (Carrier et al, 1994;Chin et al, 1997;Graunke et al, 1999;Papathanasiou et al, 1991;Zhan et al, 1993Zhan et al, , 1994, UVC irradiation Takahashi et al, 2001;Zhan et al, 1993Zhan et al, , 1998, camptothecin (Takahashi et al, 2001), or methyl methane sulphonate (Hollander et al, 1993;Zhan et al, 1998). Until now, studies of gadd45-responsiveness to DNA damage in human melanoma cell lines have used ionizing radiation or UVC irradiation as stressors (Bae et al, 1996;Haapajarvi et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that, in melanoma cells, these transcription factors are regulated at a post-translational level in response to these stressors. Interestingly, Graunke et al (1999) have also shown that octamer sites are always occupied whether the cells are treated by ionizing radiation or not. So, they suggested that this genotoxic agent up-regulates gadd45 expression by altering prebound transcription factor interactions without changing protein binding or chromatin structure.…”

Section: Discussionmentioning

confidence: 99%

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The specific activation of gadd45 following UVB radiation requires the POU family gene product N-oct3 in human melanoma cells

et al. 2001

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Here we report the speci®c regulation of gadd45 expression in human melanoma cell lines following UVB radiation. This solar wavelength is likely to be involved in melanoma aetiology. We have previously shown that gadd45 expression is strongly enhanced in a p53-independent manner following UVB irradiation, unlike the other p53 target genes studied. Furthermore, gadd45 is speci®cally activated in melanocytes since its induction in response to UVB, is not observed in other skin cells such as keratinocytes or ®broblasts. To investigate this particular regulation of gadd45, we analysed the UVB-induced response of di erent gadd45 promoter regions. Thus, a minimal promoter region of 50 bp length, responsible for gadd45 activation in melanoma cell lines following UVB irradiation, was determined. In electrophoretic mobility shift assays (EMSAs), we showed that this region (7106/756) of the gadd45 promoter which contains two identical octamers, binds the POU family gene products oct-1 and N-oct3. Given the speci®c expression pattern of Noct3 in melanocyte, we invalidated the expression of this transcription factor in melanoma cells: such an abrogation of N-oct3 protein expression in melanoma cells impeded gadd45 UVB-response. Thus the response of melanocyte to UVB may use an original and previously undescribed pathway. Oncogene (2001) 20, 7375 ± 7385.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The specific activation of gadd45 following UVB radiation requires the POU family gene product N-oct3 in human melanoma cells

et al. 2001

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“…3). These observations are virtually identical to those reported for the GADD45 promoter following IR exposure (10). Although our data cannot rule out subtle chromatin alterations at p21 and related p53-regulated promoters, they clearly do not support the contention that significant chromatin alteration is needed for p53-mediated gene activation.…”

Section: Fig 6 P53 Interacts With P53 Res In Dna-damaged Hct116 Celsupporting

confidence: 55%

Constitutive DNase I Hypersensitivity of p53-Regulated Promoters

Braastad

Han

Hendrickson

2003

Journal of Biological Chemistry

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The ability of p53 to alter, at the transcriptional level, the gene expression of downstream targets is critical for its role as a tumor suppressor. Most models of p53 activation postulate the stepwise recruitment by p53 of coactivators, histone acetyltransferases, and/or chromatin remodeling factors to a promoter region to facilitate the subsequent access of the general transcriptional machinery required for transcriptional induction. We demonstrate here, however, that the promoter regions for the p53 target genes, p21, 14-3-3, and KARP-1, exist in a constitutively open conformation that is readily accessible to DNase I. This conformation was not altered by DNA damage or by whether p53 was present or absent in the cell. In contrast, p53 response elements, which resided outside the immediate promoter regions, existed within DNase I-resistant chromatin domains. Thus, p53 activation of downstream target genes occurs without p53 inducing chromatin alterations detectable by DNase I accessibility at either the promoter or the response element. As such, these data support models of p53 activation that do not require extensive chromatin alterations to support cognate gene expression.The differential chromatin structure and nuclease accessibility at a promoter region has long been recognized as a key distinguishing feature between active and inactive genes (reviewed in Ref. 1). Almost invariably, the promoter regions of active genes are marked experimentally by hypersensitivity to restriction endonucleases (2, 3) or, more commonly, DNase I (4). Although this hypersensitivity can be caused by torsional or topological stress in the DNA and distortions in the chromatin structure resulting from transcription factor binding, it is generally caused by the absence of nucleosomes or their remodeling (1, 4). The paucity of nucleosomes, in turn, is a direct consequence of the repressive effect that nucleosomes have on the transcriptional machinery and the requirement to alleviate that effect for productive transcription to occur (5-7). Thus, inactive genes usually have promoters that are nucleosomal, are insensitive to DNase I, and are regarded as being in a closed confirmation whereas active genes usually have core promoters that are nucleosome-free, hypersensitive to DNase I, and in an open configuration. Consequently, one of the hallmarks of gene induction mechanisms is the remodeling of the nucleosomal architecture of a promoter as it is activated (5, 6, 8).Enormous strides have been made in the last decade in understanding transcriptional activation at the chromatin level. In particular, the activation of expression of many, although not all (9 -11), inducible eukaryotic genes is consistent with what can collectively be called recruitment models of gene activation (3, 7, 8) (reviewed in Ref. 12). These models usually require, in response to some extracellular cue, the induction of a specific transcription factor and the subsequent interaction of that factor with its cognate response element, which is invariably a cis-acting ...

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“…7,101 Another view of p53-depending transcriptional activation is based on the observation that the regions of chromatin within the vicinity of several p53 responsive promotes (including GADD45 and MDM2) exist in open conformations regardless of the conditions (normal versus genotoxic). [102][103][104] Constitutive hypersensitivity of these promoters to DNase I led to the suggestion that they might be nucleosome-free, and do not require significant chromatin alterations to become activated. By analogy with some genes, which are regulated by promoter proximal pausing and factors facilitating reinitiation of stalled RNA Polymerase, p53 has been suggested to induce reinitiation of transcription.…”

Section: Transcription Regulation By P53mentioning

confidence: 99%

Transcriptional regulation by p53: one protein, many possibilities

2006

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The p53 tumor suppressor protein is a DNA sequence-specific transcriptional regulator that, in response to various forms of cellular stress, controls the expression of numerous genes involved in cellular outcomes including among others, cell cycle arrest and cell death. Two key features of the p53 protein are required for its transcriptional activities: its ability to recognize and bind specific DNA sequences and to recruit both general and specialized transcriptional co-regulators. In fact, multiple interactions with co-activators and corepressors as well as with the components of the general transcriptional machinery allow p53 to either promote or inhibit transcription of different target genes. This review focuses on some of the salient features of the interactions of p53 with DNA and with factors that regulate transcription. We discuss as well the complexities of the functional domains of p53 with respect to these interactions.

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Presetting of chromatin structure and transcription factor binding poise the human GADD45 gene for rapid transcriptional up-regulation

Cited by 25 publications

References 20 publications

The specific activation of gadd45 following UVB radiation requires the POU family gene product N-oct3 in human melanoma cells

The specific activation of gadd45 following UVB radiation requires the POU family gene product N-oct3 in human melanoma cells

Constitutive DNase I Hypersensitivity of p53-Regulated Promoters

Transcriptional regulation by p53: one protein, many possibilities

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