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Updated: Feb 7, 2026

Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
Published on: July 12, 2012
Analysis of diet-induced differential methylation, expression, and interactions of lncRNA and protein-coding genes in
Jose P Silva1, Derek van Booven2
1Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA. jossil68@gmail.com.
Abstract:
Long non-coding RNAs (lncRNAs) regulate expression of protein-coding genes in cis through chromatin modifications including DNA methylation. Here we interrogated whether lncRNA genes may regulate transcription and methylation of their flanking or overlapping protein-coding genes in livers of mice exposed to a 12-week cholesterol-rich Western-style high fat diet (HFD) relative to a standard diet (STD). Deconvolution analysis of cell type-specific marker gene expression suggested similar hepatic cell type composition in HFD and STD livers. RNA-seq and validation by nCounter technology revealed differential expression of 14 lncRNA genes and 395 protein-coding genes enriched for functions in steroid/cholesterol synthesis, fatty acid metabolism, lipid localization, and circadian rhythm. While lncRNA and protein-coding genes were co-expressed in 53 lncRNA/protein-coding gene pairs, both were differentially expressed only in 4 lncRNA/protein-coding gene pairs, none of which included protein-coding genes in overrepresented pathways. Furthermore, 5-methylcytosine DNA immunoprecipitation sequencing and targeted bisulfite sequencing revealed no differential DNA methylation of genes in overrepresented pathways. These results suggest lncRNA/protein-coding gene interactions in cis play a minor role mediating hepatic expression of lipid metabolism/localization and circadian clock genes in response to chronic HFD feeding.
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