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.

中文翻译：

---

lncRNA HOTAIR 在定义人类脂肪干细胞库特异性基因表达模式中的独特作用

腰部以上的脂肪堆积是发生肥胖相关合并症的重要风险因素，与 BMI 或总脂肪量无关。破译上半身或腹部 (ABD) 和下半身或臀股 (GF) 仓库内脂肪组织前体细胞的基因调控程序对于了解它们对脂质积累、成熟和疾病风险的不同能力非常重要。先前的研究将 HOX 转录本反义基因间 RNA (HOTAIR) 鉴定为 GF 特异性 lncRNA；然而，它在脂肪组织生物学中的作用仍不清楚。使用三种不同的方法（在 GF 人类脂肪干细胞 [GF hASCs] 中沉默 HOTAIR、在 ABD hASCs 中过表达 HOTAIR 和 ChIRP-seq）来定位 GF hASC 染色质中的 HOTAIR 结合，我们发现 HOTAIR 结合并调节表达, 无论是积极的还是消极的，参与脂肪组织特异性途径的基因，包括脂肪生成。我们进一步证明了 HOTAIR 与其基因体中具有高 RNAPII 结合的基因之间的直接相互作用，特别是在它们的 3' 末端或转录末端位点。计算分析表明，HOTAIR 优先结合含有预测的与 HOTAIR 的强 RNA-RNA 相互作用的基因的 3' 端。总之，这些结果揭示了 HOTAIR 在 hASC 仓库特异性基因表达调控中的独特功能。计算分析表明，HOTAIR 优先结合含有预测的与 HOTAIR 的强 RNA-RNA 相互作用的基因的 3' 端。总之，这些结果揭示了 HOTAIR 在 hASC 仓库特异性基因表达调控中的独特功能。计算分析表明，HOTAIR 优先结合含有预测的与 HOTAIR 的强 RNA-RNA 相互作用的基因的 3' 端。总之，这些结果揭示了 HOTAIR 在 hASC 仓库特异性基因表达调控中的独特功能。