Altered huntingtin-chromatin interactions predict transcriptional and epigenetic changes in Huntington's disease.

ABSTRACT: While progressive striatal gene expression changes and epigenetic alterations are a prominent feature of Huntington's disease (HD), the mechanistic basis remains poorly understood. Using chromatin immunoprecipitation and sequencing (ChIP-seq), we show that the huntingtin protein (HTT) reproducibly occupies specific locations in the mouse genome. Striatal HTT ChIP-seq peaks were enriched in coding regions of spiny projection neuron identity genes that were found to have reduced expression in HD patients and mouse models, and had reduced occupancy in expanded polyglutamine HTT knock-in mice (HttQ111/Q111). By contrast, HTT occupancy was depleted near genes that are upregulated in HD. ChIP-seq of striatal histone modifications revealed genotype-specific colocalization of HTT with active chrom

SUBMITTER: Pearl JR 

PROVIDER: S-EPMC12147460 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature