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Neuronal methylome reveals CREB-associated neuro-axonal impairment in multiple sclerosis.


ABSTRACT: BACKGROUND:Due to limited access to brain tissue, the precise mechanisms underlying neuro-axonal dysfunction in neurological disorders such as multiple sclerosis (MS) are largely unknown. In that context, profiling DNA methylation, which is a stable and cell type-specific regulatory epigenetic mark of genome activity, offers a unique opportunity to characterize the molecular mechanisms underpinning brain pathology in situ. We examined DNA methylation patterns of neuronal nuclei isolated from post-mortem brain tissue to infer processes that occur in neurons of MS patients. RESULTS:We isolated subcortical neuronal nuclei from post-mortem white matter tissue of MS patients and non-neurological controls using flow cytometry. We examined bulk DNA methylation changes (total n =?29) and further disentangled true DNA methylation (5mC) from neuron-specific DNA hydroxymethylation (5hmC) (n =?17), using Illumina Infinium 450K arrays. We performed neuronal sub-type deconvolution using glutamate and GABA methylation profiles to further reduce neuronal sample heterogeneity. In total, we identified 2811 and 1534 significant (genome-wide adjusted P value

SUBMITTER: Kular L 

PROVIDER: S-EPMC6543588 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Neuronal methylome reveals CREB-associated neuro-axonal impairment in multiple sclerosis.

Kular Lara L   Needhamsen Maria M   Adzemovic Milena Z MZ   Kramarova Tatiana T   Gomez-Cabrero David D   Ewing Ewoud E   Piket Eliane E   Tegnér Jesper J   Beck Stephan S   Piehl Fredrik F   Brundin Lou L   Jagodic Maja M  

Clinical epigenetics 20190530 1


<h4>Background</h4>Due to limited access to brain tissue, the precise mechanisms underlying neuro-axonal dysfunction in neurological disorders such as multiple sclerosis (MS) are largely unknown. In that context, profiling DNA methylation, which is a stable and cell type-specific regulatory epigenetic mark of genome activity, offers a unique opportunity to characterize the molecular mechanisms underpinning brain pathology in situ. We examined DNA methylation patterns of neuronal nuclei isolated  ...[more]

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