p53 Binding to Nucleosomal DNA Depends on the Rotational Positioning of DNA Response Element

Sahu, Geetaram; Wang, Difei; Chen, Claudia B.; Zhurkin, Victor B.; Harrington, R. M.; Appella, Ettore; Hager, Gordon L.; Nagaich, Akhilesh K.

doi:10.1074/jbc.m109.081182

Cited by 45 publications

(56 citation statements)

References 55 publications

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“…5G). Taken together, our data thus provide a genome-wide view of TP53 and TP63 as pioneer factors, as suggested by previous observations that some TP53 binding sites are nucleosomal (Lidor Nili et al 2010;Sahu et al 2010;Laptenko et al 2011;Cui and Zhurkin 2014). We speculate that the pioneer activity of TP53 is a crucial, intrinsic property of the TP53 protein and contributes to its tumor suppressive function by allowing for discrimination of its response elements in many chromatin contexts.…”

Section: Tp53 Family Pioneer Activity At Enhancer Elementssupporting

confidence: 56%

“…S4B). This suggests that TP53 may act as a pioneer factor, binding directly to its response element in the context of a nucleosome, as was previously suggested for TP53 acting at individual binding sites (Lidor Nili et al 2010;Sahu et al 2010;Laptenko et al 2011;Cui and Zhurkin 2014). We therefore examined nucleosome enrichment using published genome-wide mononucleosome (MNase) data from IMR90 fibroblasts (Kelly et al 2012).…”

Section: Tp53 Binds To Inaccessible Chromatin Lacking H3k4 Methylationmentioning

confidence: 99%

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TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity

et al. 2014

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Despite overwhelming evidence that transcriptional activation by TP53 is critical for its tumor suppressive activity, the mechanisms by which TP53 engages the genome in the context of chromatin to activate transcription are not well understood. Using a compendium of novel and existing genome-wide data sets, we examined the relationship between TP53 binding and the dynamics of the local chromatin environment. Our analysis revealed three distinct categories of TP53 binding events that differ based on the dynamics of the local chromatin environment. The first class of TP53 binding events occurs near transcriptional start sites (TSS) and is defined by previously characterized promoter-associated chromatin modifications. The second class comprises a large cohort of preestablished, promoter-distal enhancer elements that demonstrates dynamic histone acetylation and transcription upon TP53 binding. The third class of TP53 binding sites is devoid of classic chromatin modifications and, remarkably, fall within regions of inaccessible chromatin, suggesting that TP53 has intrinsic pioneer factor activity and binds within structurally inaccessible regions of chromatin. Intriguingly, these inaccessible TP53 binding sites feature several enhancer-like properties in cell types within the epithelial lineage, indicating that TP53 binding events include a group of ''proto-enhancers'' that become active enhancers given the appropriate cellular context. These data indicate that TP53, along with TP63, may act as pioneer factors to specify epithelial enhancers. Further, these findings suggest that rather than following a global cell-type invariant stress response program, TP53 may tune its response based on the lineage-specific epigenomic landscape.

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Section: Tp53 Family Pioneer Activity At Enhancer Elementssupporting

confidence: 56%

Section: Tp53 Binds To Inaccessible Chromatin Lacking H3k4 Methylationmentioning

confidence: 99%

TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity

et al. 2014

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“…Experiments involving in vitro p53 binding to the RE localized within mononucleosome reconstituted with either H2A or H2A.Z may provide insight into the relative affinities of such substrates toward p53. A different mechanism for p53-nucleosome interaction was proposed by Sahu et al based on the results of an elegant in vitro study (30). The authors suggest that orientation of the p53 binding site on a nucleosome in conjuction with a nucleosomal positioning sequence may preset the p53 RE in a way that is easily accessible to p53.…”

Section: Localized P53-dependent Eviction Of Nucleosomes Occurs At Thmentioning

confidence: 99%

p53 binding to nucleosomes within the p21 promoter in vivo leads to nucleosome loss and transcriptional activation

Laptenko

Beckerman

Freulich

et al. 2011

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

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It is well established that p53 contacts DNA in a sequencedependent manner in order to transactivate its myriad target genes. Yet little is known about how p53 interacts with its binding site/response element (RE) within such genes in vivo in the context of nucleosomal DNA. In this study we demonstrate that both distal (5′) and proximal (3′) p53 REs within the promoter of the p21 gene in unstressed HCT116 colon carcinoma cells are localized within a region of relatively high nucleosome occupancy. In the absence of cellular stress, p53 is prebound to both p21 REs within nucleosomal DNA in these cells. Treatment of cells with the DNA-damaging drug doxorubicin or the p53 stabilizing agent Nutlin-3, however, is accompanied by p53-dependent subsequent loss of nucleosomes associated with such p53 REs. We show that in vitro p53 can bind to mononucleosomal DNA containing the distal p21 RE, provided the binding site is not close to the diad center of the nucleosome. In line with this, our data indicate that the p53 distal RE within the p21 gene is located close to the end of the nucleosome. Thus, lowand high-resolution mapping of nucleosome boundaries around p53 REs within the p21 promoter have provided insight into the mechanism of p53 binding to its sites in cells and the consequent changes in nucleosome occupancy at such sites.DNA binding | DNA damage

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“…Although the presence of TREs indicates a potential involvement of AP-1-regulated transcription, some degenerate sequences that are similar but not identical to the TRE seem to be recognized by selective AP-1 or bZIP complexes (7). This situation is further complicated by the fact that not every putative binding site is recognized by its cognate trans-acting factors, considering the dynamics of nucleosomal histones that may or may not present the sequence element in the right configuration accessible for direct protein-DNA interaction (8). Genome-wide surveys of transcription factor binding sites also uncover many cis-acting elements that do not conform to the consensus of factor binding sites (9).…”

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confidence: 99%

Binding Site Specificity and Factor Redundancy in Activator Protein-1-driven Human Papillomavirus Chromatin-dependent Transcription

Wang

Lee

et al. 2011

Journal of Biological Chemistry

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Background: Biochemical activity of dimeric AP-1 family proteins remains to be characterized. Results: 1) Binding to canonical and non-canonical sequence elements in HPV-11 is different among dimeric AP-1 family members. 2) p300-mediated acetylation is important for AP-1-dependent HPV chromatin transcription. Conclusion: Non-canonical binding sites and p300 are important for AP-1-regulated HPV transcription. Significance: Binding-site specificity and redundancy among AP-1 family members and the molecular action of p300 are now defined in vitro and in cell-based assays.

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p53 Binding to Nucleosomal DNA Depends on the Rotational Positioning of DNA Response Element

Cited by 45 publications

References 55 publications

TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity

TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity

p53 binding to nucleosomes within the p21 promoter in vivo leads to nucleosome loss and transcriptional activation

Binding Site Specificity and Factor Redundancy in Activator Protein-1-driven Human Papillomavirus Chromatin-dependent Transcription

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