GSE63675
Deficits in histone acetylation and methylation are restricted to specific loci in Huntington's disease models
The present study extends the analysis initiated in a previous report in the popular HD transgenic mouse strain N171-82Q (82Q) (Valor et al., 2013), to other diverse mHtt-expressing animal and cellular models. We show that bulk histone hypoacetylation is not a general rule. Moreover, examination of other histone post-traslational modifications led to a detailed study of the trimethylation of lysine 4 of histone H3 (H3K4me3), which is tightly associated with active genes (Lopez-Atalaya et al., 2013), by combining both single-gene and genome-wide approaches. Comparison of the 82Q and another animal model, the R6/1 strain, revealed that changes in the levels of bulk H3K4me3 may be correlated with the degree of methylation impairment for specific genes. Yet, these changes are restricted to few genomic positions. In any case, and reminiscent of the situation with histone acetylation (Valor et al., 2013; McFarland et al., 2012), deficits in histone H3 methylation do not follow a straight relationship with transcriptional dysregulation. Overall design: Genome-wide profiling by high throughput sequencing of H3K4me3 in the adult hippocampus of N171-82Q (HD) and their wild-type littermates mice (WT). Chromatin immunoprecipitation (ChIP) was carried out using pooled whole hippocampal tissue from 3 mice. DNA libraries (HD, WT, input) were constructed and single-end sequenced (1x50bp) in HiSeq 2500 platform (Illumina).