HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution
<p>Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA <em>HOTAIR</em> (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find...
| Үндсэн зохиолчид: | , , , , , , , , , , , , , , , , |
|---|---|
| Формат: | Journal article |
| Хэл сонгох: | English |
| Хэвлэсэн: |
Cell Press
2022
|
| Тойм: | <p>Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA <em>HOTAIR</em> (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 <em>HOTAIR</em>-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. <em>HOTAIR</em> is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of <em>HOTAIR</em> is maintained by defined regions of open chromatin across the <em>HOTAIR</em> promoter. <em>HOTAIR</em> expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a <em>HOTAIR</em> eQTL associated with reduced gynoid fat mass). These data identify <em>HOTAIR</em> as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.</p> |
|---|