Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease

ABSTRACT: Lamins are crucial proteins for nuclear functionality. Here, we provide new evidence showing that increased lamin B1 levels contribute to the pathophysiology of Huntington's disease (HD), a CAG repeat-associated neurodegenerative disorder. Through fluorescence-activated nuclear suspension imaging we show that nucleus from striatal medium-sized spiny and CA1 hippocampal neurons display increased lamin B1 levels, in correlation with altered nuclear morphology and nucleocytoplasmic transport disruption. Moreover, ChIP-sequencing analysis shows an alteration of lamin-associated chromatin domains in hippocampal nuclei, accompanied by changes in chromatin accessibility and transcriptional dysregulation. Supporting lamin B1 alterations as a causal role in mutant-huntingtin mediated neurodegenerat

SUBMITTER: Dr. Rafael Alcalá-Vida 

PROVIDER: S-SCDT-EMM-2020-12105 | biostudies-other |

REPOSITORIES: biostudies-other