HOTAIR Interacts with PRC2 Complex Regulating the Regional Preadipocyte Transcriptome and Human Fat Distribution

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Jul 29

PMID 35905723

Authors

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 Todorcevic

Nathan Denton

Katherine A Kentistou

Peter K Joshi

Constantinos Christodoulides

Claudia Langenberg

Philippe Collas

Fredrik Karpe

Katherine E Pinnick

Affiliations

Soon will be listed here.

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.

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