[Pao-Yang Chen] Aberrant overexpression of HOTAIR inhibits abdominal adipogenesis through remodelling of genome-wide DNA methylation and transcription

Kuo et al., 2022 Molecular Metabolism

Overexpression of HOTAIR raises the CpG methylation locating at promoters and H3K27me3 to inhibit the expression of obesity-associated genes, SLITRK4 and PITPNC1, and abdominal adipogenesis.

The long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is an important epigenetic regulator with fat depot-specific expression. Dr. Pao-Yang Chen ‘s lab collaborated with Dr. Feng-Chih Kuo from Tri-Service General Hospital to explore the functional roles of HOTAIR and its epigenetic regulation in abdominal adipogenesis. A negative correlation between adipose tissue HOTAIR expression and regional adiposity was observed. HOTAIR overexpression using human abdominal preadipocytes further revealed its anti-adipogenic effects. Integrative analysis of genome-wide DNA methylation and gene expression indicated that HOTAIR overexpression increased DNA methylation level, especially the CpG methylation locating at promoters, then reduced the gene expression. The occupancies of H3K27me3 of SLITRK4 and PITPNC1, two HOTAIR epigenetically repressed genes positively correlated with obesity, were also significantly enhanced after HOTAIR overexpression. This study demonstrated that HOTAIR is a key regulator of abdominal adipogenesis through raising DNA methylation and histone modification to inhibit obesity-associated genes and adipogenesis.

Molecular Metabolism (2022)