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

Feng-Chih Kuo1, Matt J Neville2, Rugivan Sabaratnam3

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The long non-coding RNA HOTAIR is crucial for gluteofemoral adipose tissue development. It regulates adipocyte gene expression and epigenetics, impacting regional fat distribution.

Keywords:
CP: Molecular biologyHOTAIRadipogenesisepigenetic regulationfat distributionlncRNAsubcutaneous adipose tissue

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Area of Science:

  • Genetics
  • Epigenetics
  • Molecular Biology

Background:

  • Mechanisms of regional human adipose tissue (AT) development are not fully understood.
  • The role of long non-coding RNAs (lncRNAs) in AT development is an emerging area of research.

Purpose of the Study:

  • To investigate the role of the long non-coding RNA HOTAIR in human gluteofemoral adipose tissue development.
  • To identify the molecular mechanisms by which HOTAIR regulates adipocyte differentiation and regional AT characteristics.

Main Methods:

  • Analysis of HOTAIR expression in human adipose tissue depots.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) to assess Polycomb Repressive Complex 2 (PRC2) occupancy and H3K27 trimethylation.
  • RNA sequencing to analyze the gluteal adipocyte transcriptome and alternative splicing.
  • Identification of HOTAIR expression quantitative trait loci (eQTLs) and their association with fat mass.

Main Results:

  • HOTAIR is exclusively expressed in gluteofemoral AT and is essential for adipocyte development.
  • HOTAIR interacts with PRC2 to regulate key genes in adipocyte lineage determination via promoter repression and H3K27 trimethylation.
  • HOTAIR influences the gluteal adipocyte transcriptome through alternative splicing.
  • Gluteal-specific HOTAIR expression is maintained by open chromatin regions.
  • Hormonal factors and genetic variations (e.g., rs1443512) modulate HOTAIR expression and are associated with regional fat mass.

Conclusions:

  • HOTAIR is a critical regulator of the gluteal adipocyte transcriptome and epigenome.
  • HOTAIR plays a functional role in human regional adipose tissue development.
  • Understanding HOTAIR's role provides insights into the molecular basis of regional fat distribution and potential therapeutic targets.