Dataset Information

Reversible histone glycation is associated with disease-related changes in chromatin architecture.

ABSTRACT: Cellular proteins continuously undergo non-enzymatic covalent modifications (NECMs) that accumulate under normal physiological conditions and are stimulated by changes in the cellular microenvironment. Glycation, the hallmark of diabetes, is a prevalent NECM associated with an array of pathologies. Histone proteins are particularly susceptible to NECMs due to their long half-lives and nucleophilic disordered tails that undergo extensive regulatory modifications; however, histone NECMs remain poorly understood. Here we perform a detailed analysis of histone glycation in vitro and in vivo and find it has global ramifications on histone enzymatic PTMs, the assembly and stability of nucleosomes, and chromatin architecture. Importantly, we identify a physiologic regulation mechanism, the enzyme DJ-1, which functions as a potent histone deglycase. Finally, we detect intense histone glycation and DJ-1 overexpression in breast cancer tumors. Collectively, our results suggest an additional mechanism for cellular metabolic damage through epigenetic perturbation, with implications in pathogenesis.

SUBMITTER: Zheng Q

PROVIDER: S-EPMC6426841 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Reversible histone glycation is associated with disease-related changes in chromatin architecture.

Zheng Qingfei Q Omans Nathaniel D ND Leicher Rachel R Osunsade Adewola A Agustinus Albert S AS Finkin-Groner Efrat E D'Ambrosio Hannah H Liu Bo B Chandarlapaty Sarat S Liu Shixin S David Yael Y

Nature communications 20190320 1

Cellular proteins continuously undergo non-enzymatic covalent modifications (NECMs) that accumulate under normal physiological conditions and are stimulated by changes in the cellular microenvironment. Glycation, the hallmark of diabetes, is a prevalent NECM associated with an array of pathologies. Histone proteins are particularly susceptible to NECMs due to their long half-lives and nucleophilic disordered tails that undergo extensive regulatory modifications; however, histone NECMs remain poo ...[more]

PMID: 30894531

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Project description:ObjectiveDissociative experiences commonly occur in response to trauma, and while their presence strongly affects treatment approaches in posttraumatic spectrum disorders, their etiology remains poorly understood and their phenomenology incompletely characterized. Methods to reliably assess the severity of dissociation symptoms, without relying solely on self-report, would have tremendous clinical utility. Brain-based measures have the potential to augment symptom reports, although it remains unclear whether brain-based measures of dissociation are sufficiently sensitive and robust to enable individual-level estimation of dissociation severity based on brain function. The authors sought to test the robustness and sensitivity of a brain-based measure of dissociation severity.MethodsAn intrinsic network connectivity analysis was applied to functional MRI scans obtained from 65 women with histories of childhood abuse and current posttraumatic stress disorder (PTSD). The authors tested for continuous measures of trauma-related dissociation using the Multidimensional Inventory of Dissociation. Connectivity estimates were derived with a novel machine learning technique using individually defined homologous functional regions for each participant.ResultsThe models achieved moderate ability to estimate dissociation, after controlling for childhood trauma and PTSD severity. Connections that contributed the most to the estimation mainly involved the default mode and frontoparietal control networks. By contrast, all models performed at chance levels when using a conventional group-based network parcellation.ConclusionsTrauma-related dissociative symptoms, distinct from PTSD and childhood trauma, can be estimated on the basis of network connectivity. Furthermore, between-network brain connectivity may provide an unbiased estimate of symptom severity, paving the way for more objective, clinically useful biomarkers of dissociation and advancing our understanding of its neural mechanisms.

Dataset Information

Reversible histone glycation is associated with disease-related changes in chromatin architecture.

Publications

Reversible histone glycation is associated with disease-related changes in chromatin architecture.

Similar Datasets

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