HOTAIR 通过与 PRC2 复合物相互作用调节区域性前脂肪细胞转录组和人类脂肪分布。
HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution.
机构信息
Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington OX3 7LE, UK; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defence Medical Centre, Taipei, Taiwan.
Oxford Centre for Diabetes, Endocrinology, and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Headington OX3 7LE, UK; NIHR Oxford Biomedical Research Centre, OUH Foundation Trust, Oxford, UK.
出版信息
Cell Rep. 2022 Jul 26;40(4):111136. doi: 10.1016/j.celrep.2022.111136.
Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.
调控人体脂肪组织（adipose tissue，AT）区域性发育的机制仍不清楚。本文中，我们发现长链非编码 RNA HOTAIR（HOX 转录反义 RNA）特异性表达于臀部和股部脂肪组织，对于脂肪细胞的发育是必需的。我们发现 HOTAIR 与多梳抑制复合物 2（polycomb repressive complex 2，PRC2）相互作用，并鉴定了涉及脂肪细胞谱系决定的核心 HOTAIR-PRC2 靶基因。靶基因的抑制与 PRC2 启动子占据和 H3K27 三甲基化一致。HOTAIR 还通过可变剪接参与修饰臀区脂肪细胞的转录组。HOTAIR 的臀区特异性表达由 HOTAIR 启动子上的定义明确的染色质开放区域维持。HOTAIR 的表达水平可以通过激素（雌激素、糖皮质激素）和遗传变异（rs1443512 是与女性型脂肪量减少相关的 HOTAIR 的表达数量性状基因座）进行修饰。这些数据表明 HOTAIR 是臀部脂肪细胞转录组和表观基因组的动态调控因子，对人体区域性 AT 发育具有重要功能。
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