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Exposing the core promoter is sufficient to activate transcription and alter coactivator requirement at RNR3.

ABSTRACT: Chromatin is a formidable barrier to transcription. Nucleosome density is lowest over the regulatory regions of active genes, and many repressed genes have a tightly positioned nucleosome over their core promoter. However, it has not been shown that nucleosome positioning is sufficient for repression or whether disrupting a core promoter nucleosome specifically can activate gene expression in the absence of activating signals. Here we show that disrupting the nucleosome over the core promoter of RNR3 is sufficient to drive preinitiation complex assembly and activate transcription in the absence of activating signals. Remodeling of chromatin over the RNR3 promoter requires the recruitment of the SWI/SNF complex by the general transcription factor TFIID. We found that disrupting the nucleosome over the RNR3 core promoter relieves its dependence on TFIID and SWI/SNF, indicating a functional link between these two complexes. These results suggest that the specific function of TAF(II)s is to direct the chromatin remodeling step through SWI/SNF recruitment, and not core promoter selectivity. Our results indicate that nucleosome placement plays a dominant role in repression and that the ability of the core promoter to position a nucleosome is a major determinant in TAF(II) dependency of genes in vivo.

SUBMITTER: Zhang H

PROVIDER: S-EPMC1885588 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Exposing the core promoter is sufficient to activate transcription and alter coactivator requirement at RNR3.

Zhang Hesheng H Reese Joseph C JC

Proceedings of the National Academy of Sciences of the United States of America 20070514 21

Chromatin is a formidable barrier to transcription. Nucleosome density is lowest over the regulatory regions of active genes, and many repressed genes have a tightly positioned nucleosome over their core promoter. However, it has not been shown that nucleosome positioning is sufficient for repression or whether disrupting a core promoter nucleosome specifically can activate gene expression in the absence of activating signals. Here we show that disrupting the nucleosome over the core promoter of ...[more]

PMID: 17502614

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Project description:Single-nucleotide polymorphisms (SNPs) located in the promoter region of the receptor for advanced glycation end products (RAGE) gene have been linked to the activity of RAGE. However, contrary to our expectation, we previously detected no correlation between SNPs within the RAGE promoter and ulcerative colitis (UC) risk in a case-control study. Here, we investigated the methylation of the RAGE promoter and analyzed the collective contribution of methylation and SNPs to UC risk. We found that RAGE promoter hypomethylation was more common in UC patients compared to controls (70% vs. 30%, respectively), as determined via bisulfite sequencing PCR (BSP) and methylation-specific PCR (MSP). Furthermore, we investigated the cooperativity of promoter methylation and SNPs and found that either of two SNPs (rs1800624 or rs1800625) and promoter methylation jointly contributed to UC risk (30 UC patients vs. 30 controls, P?<?0.05). There was no correlation between UC risk and either methylation or SNPs when analyzed separately. This lack of correlation is likely due to promoter methylation repressing gene transcription, whereas SNPs in the RAGE promoter region activate RAGE transcription. We found that variant allele carriers with promoter hypomethylation were at an increased risk for UC (rs1800624, OR = 10, 95% CI: 1.641-60.21, P?=?0.009; rs1800625, OR = 4.8, 95% CI: 1.074-21.447, P?=?0.039). Furthermore, our data revealed that the RAGE mRNA levels in variant allele carriers with promoter hypomethylation were significantly higher compared to those with promoter hypermethylation (P?<?0.05) as well as to those in wild-type allele individuals exhibiting promoter hypomethylation (P?<?0.05). We therefore speculate that the methylation status and SNPs present in the RAGE promoter region alter RAGE transcription, thereby impacting UC risk. We also propose that the methylation status and RAGE promoter genotype could jointly serve as clinical biomarkers to assist in UC risk assessment.

Project description:BackgroundAcetylation of promoter nucleosomes is tightly correlated and mechanistically linked to gene activity. However, transcription is not necessary for promoter acetylation. It seems, therefore, that external and endogenous stimuli control histone acetylation and by this contribute to gene regulation. Photosynthetic genes in plants are excellent models with which to study the connection between stimuli and chromatin modifications because these genes are strongly expressed and regulated by multiple stimuli that are easily manipulated. We have previously shown that acetylation of specific histone lysine residues on the photosynthetic phosphoenolpyruvate carboxylase (Pepc) promoter in maize is controlled by light and is independent of other stimuli or gene activity. Acetylation of upstream promoter regions responds to a set of other stimuli which include the nutrient availability of the plant. Here, we have extended these studies by analysing histone acetylation during the diurnal and circadian rhythm of the plant.ResultsWe show that histone acetylation of individual lysine residues is removed from the core promoter before the end of the illumination period which is an indication that light is not the only factor influencing core promoter acetylation. Deacetylation is accompanied by a decrease in gene activity. Pharmacological inhibition of histone deacetylation is not sufficient to prevent transcriptional repression, indicating that deacetylation is not controlling diurnal gene regulation. Variation of the Pepc promoter activity during the day is controlled by the circadian oscillator as it is maintained under constant illumination for at least 3 days. During this period, light-induced changes in histone acetylation are completely removed from the core promoter, although the light stimulus is continuously applied. However, acetylation of most sites on upstream promoter elements follows the circadian rhythm.ConclusionOur results suggest a central role of upstream promoter acetylation in the quantitative regulation of gene expression in this model gene. Induced core promoter acetylation is dispensable for the highest gene expression in the diurnal and circadian rhythm.

Dataset Information

Exposing the core promoter is sufficient to activate transcription and alter coactivator requirement at RNR3.

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Exposing the core promoter is sufficient to activate transcription and alter coactivator requirement at RNR3.

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