Temporal gene regulation by p53 is associated with the rotational setting of its binding motifs in nucleosomes
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ABSTRACT:
PROVIDER: PRJNA660785 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12566302.fastq.gz | Fastqsanger.gz | |||
| SRR12566303.fastq.gz | Fastqsanger.gz | |||
| SRR12566304.fastq.gz | Fastqsanger.gz | |||
| SRR12566305.fastq.gz | Fastqsanger.gz | |||
| SRR12566306.fastq.gz | Fastqsanger.gz |
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Project description:The precise mechanisms governing sequence-dependent positioning of nucleosomes on DNA remain unknown in detail. Existing algorithms, taking into account the sequence-dependent deformability of DNA and its interactions with the histone globular domains, predict rotational setting of only 65% of human nucleosomes mapped in vivo. To uncover novel factors responsible for the nucleosome positioning, we analyzed potential involvement of the histone N-tails in this process. To this aim, we reconstituted the H2A/H4 N-tailless nucleosomes on human BRCA1 DNA (~100 kb) and compared their positions and sequences with those of the wild-type nucleosomes. In the case of H2A tailless nucleosomes, the AT content of DNA sequences is changed locally at superhelical location (SHL) ±4, while maintaining the same rotational setting as their wild-type counterparts. Conversely, the H4 tailless nucleosomes display widespread changes of the AT content near SHL ±1 and SHL ±2, where the H4 N-tails interact with DNA. Furthermore, a substantial number of H4 tailless nucleosomes exhibit rotational setting opposite to that of the wild-type nucleosomes. Thus, our findings strongly suggest that the histone N-tails are operative in selection of nucleosome positions, which may have wide-ranging implications for epigenetic modulation of chromatin states.
2024-01-03 | GSE252427 | GEO
Project description:HCT116 cells treated with 5-FU along with DMSO and non-treatment controls using time-course RNA-seq were used to investigate target genes regulated by p53 at the different timepoints.
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Project description:Plant and animal centromeres comprise megabases of highly repeated satellite sequences, yet centromere function can be specified epigenetically on single-copy DNA by the presence of nucleosomes containing a centromere-specific variant of histone H3 (cenH3). We determined the positions of cenH3 nucleosomes in rice (Oryza sativa), which has centromeres composed of both the 155-bp CentO repeat and single-copy non-CentO sequences. We find that cenH3 nucleosomes protect 90-100 bp of DNA from micrococcal nuclease digestion, sufficient for only a single wrap of DNA around the cenH3 nucleosome core. cenH3 nucleosomes are translationally phased with 155-bp periodicity on CentO repeats, but not on non-CentO sequences. CentO repeats have a ~10-bp periodicity in WW dinucleotides and in micrococcal nuclease cleavage, providing evidence for rotational phasing of cenH3 nucleosomes on CentO, and suggesting that satellites evolve for translational and rotational stabilization of centromeric nucleosomes. Examination of measured size of rice centromere nucleosome
2013-11-06 | E-GEOD-50755 | biostudies-arrayexpress
Project description:Plant and animal centromeres comprise megabases of highly repeated satellite sequences, yet centromere function can be specified epigenetically on single-copy DNA by the presence of nucleosomes containing a centromere-specific variant of histone H3 (cenH3). We determined the positions of cenH3 nucleosomes in rice (Oryza sativa), which has centromeres composed of both the 155-bp CentO repeat and single-copy non-CentO sequences. We find that cenH3 nucleosomes protect 90-100 bp of DNA from micrococcal nuclease digestion, sufficient for only a single wrap of DNA around the cenH3 nucleosome core. cenH3 nucleosomes are translationally phased with 155-bp periodicity on CentO repeats, but not on non-CentO sequences. CentO repeats have a ~10-bp periodicity in WW dinucleotides and in micrococcal nuclease cleavage, providing evidence for rotational phasing of cenH3 nucleosomes on CentO, and suggesting that satellites evolve for translational and rotational stabilization of centromeric nucleosomes.
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Project description:The tumor suppressor protein p53 is a DNA-binding transcription factor (TF) that, once activated, coordinates the expression of thousands of target genes. Increased p53 binding to gene promoters occurs shortly after p53 activation. Intriguingly, gene transcription exhibits differential kinetics with some genes being induced early (early genes) and others being induced late (late genes). To understand pre-binding factors contributing to the temporal gene regulation by p53, we performed time-course RNA sequencing experiments in human colon cancer cell line HCT116 treated with fluorouracil to identify early and late genes. Published p53 ChIP fragments co-localized with the early or late genes were used to uncover p53 binding sites (BS). We demonstrate that the BS associated with early genes are clustered around gene starts with decreased nucleosome occupancy. DNA analysis shows that these BS are likely exposed on nucleosomal surface if wrapped into nucleosomes, thereby facilitating stable interactions with and fast induction by p53. By contrast, p53 BS associated with late genes are distributed uniformly across the genes with increased nucleosome occupancy. Predicted rotational settings of these BS show limited accessibility. We therefore propose a hypothetical model in which the BS are fully, partially or not accessible to p53 in the nucleosomal context. The partial accessibility of the BS allows subunits of a p53 tetramer to bind, but the resulting p53-DNA complex may not be stable enough to recruit cofactors, which leads to delayed induction. Our work highlights the importance of DNA conformations of p53 BS in gene expression dynamics.
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Project description:Nucleosome organization determines chromatin state, which subsequently controls genes expression or silencing. Nucleosome remodeling occurs during somatic cell reprogramming, but it remains undetermined to what degree the re-established nucleosome organization resembles between induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs). Here, we generated genome-wide maps of nucleosomes in mouse ESCs and iPSCs reprogrammed from somatic cells belonging to three different germ layers using a secondary reprogramming system. Pairwise comparisons show that nucleosome organization is nearly identical between ESCs and iPSCs regardless of the iPSCs’ tissue of origin. A distinct nucleosome occupancy pattern was observed at silent transcriptional units. Transcription factor binding sites possess characteristic nucleosomal architecture such that their access is governed under rotational setting and translational setting accordingly. Gene expression profiles further reveal that the transcriptional programs are highly correlated between iPSCs and ESCs. These findings indicate that nucleosome organizations can be accurately remodeled during nuclear reprogramming. Gene expression profiles of 5 cell lines with or without biological replicates
2014-12-09 | E-GEOD-46716 | biostudies-arrayexpress
Project description:DNA-targeting drugs may damage DNA or chromatin. Many anti-cancer drugs do both, making difficult understanding their mechanism of actions. Using molecules causing DNA breaks without altering nucleosome structure (bleomycin) or destabilizing nucleosomes without damaging DNA (curaxin), we investigated consequences of DNA or chromatin damage in normal and tumor cells. As expected, DNA damage caused p53-dependent growth arrest followed by senescence. Chromatin damage caused higher p53 accumulation than DNA damage, but growth arrest was p53-independent and did not result in senescence. Chromatin damage activated transcription of multiple genes, including classical p53 targets, in a p53-independent manner. These activated genes, though they were not highly expressed, have chromatin organization around transcription start sites (TSS) characteristic for the most highly expressed genes and the highest level of paused RNA polymerase. We proposed that nucleosomes around TSS of these genes are the most sensitive to chromatin damage, and therefore nucleosome loss upon curaxin treatment enables transcription without assistance of sequence-specific transcriptional factors. We confirmed this by showing greater loss of nucleosomes around TSS of these genes upon curaxin treatment and activation of specific p53 reporter in p53-null cells by chromatin damaging agents, but not DNA damaging agents.
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Project description:We assess the role of intrinsic histone-DNA interactions by mapping nucleosomes assembled in vitro on genomic DNA. Nucleosomes strongly prefer yeast DNA over E. coli DNA, indicating that the yeast genome evolved to favor nucleosome formation. Many yeast promoter and terminator regions intrinsically disfavor nucleosome formation, and nucleosomes assembled in vitro display strong rotational positioning. Nucleosome arrays generated by the ACF assembly factor display fewer nucleosome-free regions, reduced rotational positioning, and less translational positioning than obtained by intrinsic histone-DNA interactions. Importantly, in vitro assembled nucleosomes display only a limited preference for specific translational positions and do not show the pattern observed in vivo. Our results argue against a genomic code for nucleosome positioning, and they suggest that the nucleosomal pattern in coding regions arises primarily from statistical positioning from a barrier near the promoter that involves some aspect of transcriptional initiation by RNA polymerase II.
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Project description:UV-induced DNA lesions are an important contributor to mutagenesis and cancer, but it is not fully understood how the chromosomal landscape influences UV lesion formation and repair. We have used a novel high-throughput sequencing method to precisely map UV-induced cyclobutane pyrimidine dimers (CPDs) at nucleotide resolution throughout the yeast genome. Analysis of CPD formation reveals that nucleosomal DNA having an inward rotational setting is protected from CPD lesions. In strongly positioned nucleosomes, this nucleosome 'photofootprint' overrides intrinsic dipyrimidine sequence preferences for CPD formation. CPD formation is also inhibited by DNA-bound transcription factors, in effect protecting important DNA elements from UV damage. Analysis of CPD repair revealed a clear signature of efficient transcription-coupled nucleotide excision repair. Repair was less efficient at translational positions near a nucleosome dyad and at heterochromatic regions in the yeast genome. These findings define the roles of nucleosomes and transcription factors in UV damage formation and repair. UV mapping data was analyzed for yeast cells irradiated with 125J/m2 and allowed to repair for 0hr (2 samples), 20 minutes, 1 hour, or 2 hours. Data is also included for naked DNA irradiated with UV 60 or 90 J/m2
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