Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes

Brown, Amber N.; Vied, Cynthia; Dennis, Jane A; Bhide, Pradeep G.

doi:10.1371/journal.pone.0139103

Cited by 12 publications

(7 citation statements)

References 60 publications

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“…Interestingly, recent studies show that when trans- factors are massively malfunctioning—e.g. in early stages of cancer progression ( 50 ), upon viral infection ( 51 ) or upon drug treatments ( 52 )—DNA sequence plays a more prominent role in determining nucleosome redistribution, highlighting the need for a computational model that can account for the dynamic interplay between trans-acting proteins and intrinsic DNA sequence to explain the regulation of local chromatin structure. This paper takes a stride toward this goal and provides a general computational framework for quantifying the presence of hidden periodic sequence features and relating these features to distinct characteristics of nucleosome positioning.…”

Section: Discussionmentioning

confidence: 99%

Categorical spectral analysis of periodicity in nucleosomal DNA

Rube

Song

2016

Nucleic Acids Res

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DNA helical twist imposes geometric constraints on the location of histone–DNA interaction sites along nucleosomal DNA. Certain 10.5-bp periodic nucleotides in phase with these geometric constraints have been suggested to facilitate nucleosome positioning. However, the extent of nucleotide periodicity in nucleosomal DNA and its significance in directing nucleosome positioning still remain unclear. We clarify these issues by applying categorical spectral analysis to high-resolution nucleosome maps in two yeast species. We find that only a small fraction of nucleosomal sequences contain significant 10.5-bp periodicity. We further develop a spectral decomposition method to show that the previously observed periodicity in aligned nucleosomal sequences mainly results from proper phasing among nucleosomal sequences, and not from a preponderant occurrence of periodicity within individual sequences. Importantly, we show that this phasing may arise from the histones’ proclivity for putting preferred nucleotides at some of the evenly spaced histone–DNA contact points with respect to the dyad axis. We demonstrate that 10.5-bp periodicity, when present, significantly facilitates rotational, but not translational, nucleosome positioning. Finally, although periodicity only moderately affects nucleosome occupancy genome wide, reduced periodicity is an evolutionarily conserved signature of nucleosome-depleted regions around transcription start/termination sites.

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Section: Discussionmentioning

confidence: 99%

Categorical spectral analysis of periodicity in nucleosomal DNA

Rube

Song

2016

Nucleic Acids Res

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“…The analysis yielded a list of mRNAs present at significantly different levels between the aspartame and plain drinking water groups and provided a measure of confidence of each difference. Genes with a statistically significant differential expression were further analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using Webgestalt ( 82 , 83 ) to establish possible functional roles ( 84 – 87 ). All data from these analyses are available in the NCBI Gene Expression Omnibus https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE210561 (Accession # accession GSE210561).…”

Section: Methodsmentioning

confidence: 99%

Transgenerational transmission of aspartame-induced anxiety and changes in glutamate-GABA signaling and gene expression in the amygdala

Jones

McCarthy

Vied

et al. 2022

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

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We report the effects of aspartame on anxiety-like behavior, neurotransmitter signaling and gene expression in the amygdala, a brain region associated with the regulation of anxiety and fear responses. C57BL/6 mice consumed drinking water containing 0.015% or 0.03% aspartame, a dose equivalent of 8 to 15% of the FDA recommended maximum human daily intake, or plain drinking water. Robust anxiety-like behavior (evaluated using open field test and elevated zero maze) was observed in male and female mice consuming the aspartame-containing water. Diazepam, an allosteric modulator of the GABA-A receptor, alleviated the anxiety-like behavior. RNA sequencing of the amygdala followed by KEGG biological pathway analysis of differentially expressed genes showed glutamatergic and GABAergic synapse pathways as significantly enriched. Quantitative PCR showed upregulation of mRNA for the glutamate NMDA receptor subunit 2D ( Grin2d ) and metabotropic receptor 4 ( Grm4 ) and downregulation of the GABA-A receptor associated protein ( Gabarap ) mRNA. Thus, taken together, our diazepam and gene expression data show that aspartame consumption shifted the excitation-inhibition equilibrium in the amygdala toward excitation. Even more strikingly, the anxiety-like behavior, its response to diazepam, and changes in amygdala gene expression were transmitted to male and female offspring in two generations descending from the aspartame-exposed males. Extrapolation of the findings to humans suggests that aspartame consumption at doses below the FDA recommended maximum daily intake may produce neurobehavioral changes in aspartame-consuming individuals and their descendants. Thus, human population at risk of aspartame’s potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals.

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“…Notably, the identified transcription factors were particularly driven by the Ctx condition in the NAc core, suggesting elevated transcriptional regulation. We identified enriched putative motifs for ZNF263 (Ctx group) and RRBE1 (HC group), proteins previously associated with drug exposure 46,47 (Fig. 5B, left/middle panels).…”

Section: Resultsmentioning

confidence: 96%

Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens

Martínez-Rivera,

Holt,

Minier-Toribio

et al. 2024

Preprint

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Substance use disorder is characterized by a maladaptive imbalance wherein drug seeking persists despite negative consequences or drug unavailability. This imbalance correlates with neurobiological alterations some of which are amplified during forced abstinence, thereby compromising the capacity of extinction-based approaches to prevent relapse. Cocaine use disorder (CUD) exemplifies this phenomenon in which neurobiological modifications hijack brain reward regions such as the nucleus accumbens (NAc) to manifest craving and withdrawal-like symptoms. While increasing evidence links transcriptional changes in the NAc to specific phases of addiction, genome-wide changes in gene expression during withdrawal vs. extinction (WD/Ext) have not been examined in a context- and NAc-subregion-specific manner. Here, we used cocaine self-administration (SA) in rats combined with RNA-sequencing (RNA-seq) of NAc subregions (core and shell) to transcriptionally profile the impact of experiencing withdrawal in the home cage or in the previous drug context or experiencing extinction training. As expected, home-cage withdrawal maintained drug seeking in the previous drug context, whereas extinction training reduced it. By contrast, withdrawal involving repetitive exposure to the previous drug context increased drug-seeking behavior. Bioinformatic analyses of RNA-seq data revealed gene expression patterns, networks, motifs, and biological functions specific to these behavioral conditions and NAc subregions. Comparing transcriptomic analysis of the NAc of patients with CUD highlighted conserved gene signatures, especially with rats that were repetitively exposed to the previous drug context. Collectively, these behavioral and transcriptional correlates of several withdrawal-extinction settings reveal fundamental and translational information about potential molecular mechanisms to attenuate drug-associated memories.

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Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes

Cited by 12 publications

References 60 publications

Categorical spectral analysis of periodicity in nucleosomal DNA

Categorical spectral analysis of periodicity in nucleosomal DNA

Transgenerational transmission of aspartame-induced anxiety and changes in glutamate-GABA signaling and gene expression in the amygdala

Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens

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