HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution

Feng Chih Kuo; Matt J. Neville; Rugivan Sabaratnam; Agata Wesolowska-Andersen; Daniel Phillips; Laura B.L. Wittemans; Andrea D. van Dam; Nellie Y. Loh; Marijana Todorčević; Nathan Denton; Katherine A. Kentistou; Peter K. Joshi; Constantinos Christodoulides; Claudia Langenberg; Philippe Collas; Fredrik Karpe; Katherine E. Pinnick

doi:10.1016/j.celrep.2022.111136

HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution

Feng Chih Kuo, Matt J. Neville, Rugivan Sabaratnam, Agata Wesolowska-Andersen, Daniel Phillips, Laura B.L. Wittemans, Andrea D. van Dam, Nellie Y. Loh, Marijana Todorčević, Nathan Denton, Katherine A. Kentistou, Peter K. Joshi, Constantinos Christodoulides, Claudia Langenberg, Philippe Collas, Fredrik Karpe^*, Katherine E. Pinnick

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

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.

Original language	English
Article number	111136
Journal	Cell Reports
Volume	40
Issue number	4
Number of pages	23
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2022.111136
Publication status	Published - 26. Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Keywords

adipogenesis
CP: Molecular biology
epigenetic regulation
fat distribution
HOTAIR
lncRNA
subcutaneous adipose tissue

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10.1016/j.celrep.2022.111136Licence: CC BY

Open Access VersionFinal published version, 3.86 MBLicence: CC BY

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Kuo, F. C., Neville, M. J., Sabaratnam, R., Wesolowska-Andersen, A., Phillips, D., Wittemans, L. B. L., van Dam, A. D., Loh, N. Y., Todorčević, M., Denton, N., Kentistou, K. A., Joshi, P. K., Christodoulides, C., Langenberg, C., Collas, P., Karpe, F., & Pinnick, K. E. (2022). HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution. Cell Reports, 40(4), Article 111136. https://doi.org/10.1016/j.celrep.2022.111136

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title = "HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution",

abstract = "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.",

keywords = "adipogenesis, CP: Molecular biology, epigenetic regulation, fat distribution, HOTAIR, lncRNA, subcutaneous adipose tissue",

author = "Kuo, {Feng Chih} and Neville, {Matt J.} and Rugivan Sabaratnam and Agata Wesolowska-Andersen and Daniel Phillips and Wittemans, {Laura B.L.} and {van Dam}, {Andrea D.} and Loh, {Nellie Y.} and Marijana Todor{\v c}evi{\'c} and Nathan Denton and Kentistou, {Katherine A.} and Joshi, {Peter K.} and Constantinos Christodoulides and Claudia Langenberg and Philippe Collas and Fredrik Karpe and Pinnick, {Katherine E.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = jul,

day = "26",

doi = "10.1016/j.celrep.2022.111136",

language = "English",

volume = "40",

journal = "Cell Reports",

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Kuo, FC, 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 2022, 'HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution', Cell Reports, vol. 40, no. 4, 111136. https://doi.org/10.1016/j.celrep.2022.111136

TY - JOUR

T1 - HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution

AU - Kuo, Feng Chih

AU - Neville, Matt J.

AU - Sabaratnam, Rugivan

AU - Wesolowska-Andersen, Agata

AU - Phillips, Daniel

AU - Wittemans, Laura B.L.

AU - van Dam, Andrea D.

AU - Loh, Nellie Y.

AU - Todorčević, Marijana

AU - Denton, Nathan

AU - Kentistou, Katherine A.

AU - Joshi, Peter K.

AU - Christodoulides, Constantinos

AU - Langenberg, Claudia

AU - Collas, Philippe

AU - Karpe, Fredrik

AU - Pinnick, Katherine E.

PY - 2022/7/26

Y1 - 2022/7/26

N2 - 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.

AB - 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.

KW - adipogenesis

KW - CP: Molecular biology

KW - epigenetic regulation

KW - fat distribution

KW - HOTAIR

KW - lncRNA

KW - subcutaneous adipose tissue

U2 - 10.1016/j.celrep.2022.111136

DO - 10.1016/j.celrep.2022.111136

M3 - Journal article

C2 - 35905723

AN - SCOPUS:85135087683

SN - 2211-1247

VL - 40

JO - Cell Reports

JF - Cell Reports

IS - 4

M1 - 111136

ER -

HOTAIR interacts with PRC2 complex regulating the regional preadipocyte transcriptome and human fat distribution

Abstract

Bibliographical note

Keywords

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