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...
| Huvudupphovsmän: | , , , , , , , , , , , , , , , , |
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| Materialtyp: | Journal article |
| Språk: | English |
| Publicerad: |
Cell Press
2022
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| _version_ | 1826310190071283712 |
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| author | Kuo, F-C Neville, MJ Sabaratnam, R Wesolowska-Andersen, A Phillips, D Wittemans, LBL van Dam, AD Loh, NY Todorčević, M Denton, N Kentistou, KA Joshi, PK Christodoulides, C Langenberg, C Collas, P Karpe, F Pinnick, KE |
| author_facet | Kuo, F-C Neville, MJ Sabaratnam, R Wesolowska-Andersen, A Phillips, D Wittemans, LBL van Dam, AD Loh, NY Todorčević, M Denton, N Kentistou, KA Joshi, PK Christodoulides, C Langenberg, C Collas, P Karpe, F Pinnick, KE |
| author_sort | Kuo, F-C |
| collection | OXFORD |
| description | <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> |
| first_indexed | 2024-03-07T07:46:54Z |
| format | Journal article |
| id | oxford-uuid:66e6bb21-02b6-498c-bd7a-7b29939970f4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:46:54Z |
| publishDate | 2022 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:66e6bb21-02b6-498c-bd7a-7b29939970f42023-06-21T14:50:30ZHOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distributionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:66e6bb21-02b6-498c-bd7a-7b29939970f4EnglishSymplectic ElementsCell Press2022Kuo, F-CNeville, MJSabaratnam, RWesolowska-Andersen, APhillips, DWittemans, LBLvan Dam, ADLoh, NYTodorčević, MDenton, NKentistou, KAJoshi, PKChristodoulides, CLangenberg, CCollas, PKarpe, FPinnick, KE<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> |
| spellingShingle | Kuo, F-C Neville, MJ Sabaratnam, R Wesolowska-Andersen, A Phillips, D Wittemans, LBL van Dam, AD Loh, NY Todorčević, M Denton, N Kentistou, KA Joshi, PK Christodoulides, C Langenberg, C Collas, P Karpe, F Pinnick, KE HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution |
| title | HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution |
| title_full | HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution |
| title_fullStr | HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution |
| title_full_unstemmed | HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution |
| title_short | HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution |
| title_sort | hotair interacts with prc2 complex regulating the regional preadipocyte transcriptome and human fat distribution |
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