Unique role for lncRNA HOTAIR in defining depot-specific gene expression patterns in human adipose-derived stem cells
Open Access
- 1 May 2022
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Journal of Bone and Joint Surgery
- Vol. 36 (9-10), 566-581
- https://doi.org/10.1101/gad.349393.122
Abstract
Accumulation of fat above the waist is an important risk factor in developing obesity-related comorbidities independently of BMI or total fat mass. Deciphering the gene regulatory programs of the adipose tissue precursor cells within upper body or abdominal (ABD) and lower body or gluteofemoral (GF) depots is important to understand their differential capacity for lipid accumulation, maturation, and disease risk. Previous studies identified the HOX transcript antisense intergenic RNA (HOTAIR) as a GF-specific lncRNA; however, its role in adipose tissue biology is still unclear. Using three different approaches (silencing of HOTAIR in GF human adipose-derived stem cells [GF hASCs], overexpression of HOTAIR in ABD hASCs, and ChIRP-seq) to localize HOTAIR binding in GF hASC chromatin, we found that HOTAIR binds and modulates expression, both positively and negatively, of genes involved in adipose tissue-specific pathways, including adipogenesis. We further demonstrate a direct interaction between HOTAIR and genes with high RNAPII binding in their gene bodies, especially at their 3′ ends or transcription end sites. Computational analysis suggests HOTAIR binds preferentially to the 3′ ends of genes containing predicted strong RNA–RNA interactions with HOTAIR. Together, these results reveal a unique function for HOTAIR in hASC depot-specific regulation of gene expression.Keywords
Funding Information
- National Institutes of Health (R01DK107009-02)
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