Dataset Information

Challenges in Quantifying Cytosine Methylation in the HIV Provirus.

ABSTRACT: DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. While it is clear that DNA methylation can silence HIV proviral expression in in vitro latency models, its correlation with HIV persistence and expression in vivo is ambiguous, particularly in persons living with HIV (PLWH) receiving antiretroviral therapy (ART). Several factors potentially contribute to discrepancies between results in the literature, including differences in integration sites, functional proviral load, sampling bias, and stochastic PCR amplification. Recent studies into genomic features of cytosine methylation sites in mammalian genes offer potentially significant insights into this mechanism. Here, we discuss the importance of these factors in the context of the HIV.

SUBMITTER: LaMere SA

PROVIDER: S-EPMC6343035 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Challenges in Quantifying Cytosine Methylation in the HIV Provirus.

LaMere Sarah A SA Chaillon Antoine A Huynh Christina C Smith Davey M DM Gianella Sara S

mBio 20190122 1

DNA methylation is an epigenetic mechanism most commonly associated with transcriptional repression. While it is clear that DNA methylation can silence HIV proviral expression in <i>in vitro</i> latency models, its correlation with HIV persistence and expression <i>in vivo</i> is ambiguous, particularly in persons living with HIV (PLWH) receiving antiretroviral therapy (ART). Several factors potentially contribute to discrepancies between results in the literature, including differences in integ ...[more]

PMID: 30670613

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Project description:Cytosine DNA methylation (CDM) is a stable epigenetic modification to the genome and a widespread regulatory process in living organisms that involves multicomponent molecular machines. Genome-wide cytosine methylation patterning participates in the epigenetic reprogramming of a cell, suggesting that the biological information contained within methylation positions may be amenable to decoding. Adaptation to a new cellular or organismal environment also implies the potential for genome-wide redistribution of CDM changes that will ensure the stability of DNA molecules. This raises the question of whether or not we would be able to sort out the regulatory methylation signals from the CDM background ("noise") induced by thermal fluctuations. Here, we propose a novel statistical and information thermodynamic description of the CDM changes to address the last question. The physical basis of our statistical mechanical model was evaluated in two respects: 1) the adherence to Landauer's principle, according to which molecular machines must dissipate a minimum energy ? = kBT ln2 at each logic operation, where kB is the Boltzmann constant, and T is the absolute temperature and 2) whether or not the binary stretch of methylation marks on the DNA molecule comprise a language of sorts, properly constrained by thermodynamic principles. The study was performed for genome-wide methylation data from 152 ecotypes and 40 trans-generational variations of Arabidopsis thaliana and 93 human tissues. The DNA persistence length, a basic mechanical property altered by CDM, was estimated with values from 39 to 66.9 nm. Classical methylome analysis can be retrieved by applying information thermodynamic modelling, which is able to discriminate signal from noise. Our finding suggests that the CDM signal comprises a language scheme properly constrained by molecular thermodynamic principles, which is part of an epigenomic communication system that obeys the same thermodynamic rules as do current human communication systems.

Dataset Information

Challenges in Quantifying Cytosine Methylation in the HIV Provirus.

Publications

Challenges in Quantifying Cytosine Methylation in the HIV Provirus.

Similar Datasets

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