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Biophysical studies of cholesterol effects on chromatin.

ABSTRACT: Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol's action on chromatin structure have remained unclear. Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin fibers reconstituted in vitro and characterized in silico the cholesterol binding to the nucleosome. Our findings support that cholesterol assists 10 and 30 nm chromatin formation and induces folding of long chromatin fibers as a result of direct interaction of the cholesterol to six nucleosomal binding sites.

SUBMITTER: Silva ITG

PROVIDER: S-EPMC5408612 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Biophysical studies of cholesterol effects on chromatin.

Silva Isabel T G ITG Fernandes Vinícius V Souza Caio C Treptow Werner W Santos Guilherme M GM

Journal of lipid research 20170322 5

Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol's action on chromatin structure have remained unclear. Here, we e ...[more]

PMID: 28331000

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Project description:The application of nanoparticles (NPs) in medicine and biology has received great interest due to their novel features. However, their adverse effects on the biological system are not well understood.This study aims to evaluate the effect of cerium oxide nanoparticles (CNPs) on conformational changes of human hemoglobin (HHb) and lymphocytes by different spectroscopic (intrinsic and synchronous fluorescence spectroscopy and far and near circular dichroism [CD] spectroscopy), docking and cellular (MTT and flow cytometry) investigations.Transmission electron microscopy (TEM) showed that CNP diameter is ~30 nm. The infrared spectrum demonstrated a strong band around 783 cm-1 corresponding to the CNP stretching bond. Fluorescence data revealed that the CNP is able to quench the intrinsic fluorescence of HHb through both dynamic and static quenching mechanisms. The binding constant (Kb ), number of binding sites (n), and thermodynamic parameters over three different temperatures indicated that hydrophobic interactions might play a considerable role in the interaction of CNPs with HHb. Synchronous fluorescence spectroscopy indicated that microenvironmental changes around Trp and Tyr residues remain almost unchanged. CD studies displayed that the regular secondary structure of HHb had no significant changes; however, the quaternary structure of protein is subjected to marginal structural changes. Docking studies showed the larger CNP cluster is more oriented toward experimental data, compared with smaller counterparts. Cellular assays revealed that CNP, at high concentrations (>50 µg/mL), initiated an antiproliferative response through apoptosis induction on lymphocytes.The findings may exhibit that, although CNPs did not significantly perturb the native conformation of HHb, they can stimulate some cellular adverse effects at high concentrations that may limit the medicinal and biological application of CNPs. In other words, CNP application in biological systems should be done at low concentrations.

Dataset Information

Biophysical studies of cholesterol effects on chromatin.

Publications

Biophysical studies of cholesterol effects on chromatin.

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