論文

査読有り
2019年4月8日

Genomic and epigenomic mapping of leptin-responsive neuronal populations involved in body weight regulation

Nature Metabolism
  • Fumitaka Inoue
  • ,
  • Walter L. Eckalbar
  • ,
  • Yi Wang
  • ,
  • Karl K. Murphy
  • ,
  • Navneet Matharu
  • ,
  • Christian Vaisse
  • ,
  • Nadav Ahituv

担当区分
筆頭著者
1
4
開始ページ
475
終了ページ
484
DOI
10.1038/s42255-019-0051-x

© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Genome-wide association studies in obesity have identified a large number of non-coding loci located near genes expressed in the central nervous system. However, due to the difficulties in isolating and characterizing specific neuronal subpopulations, few obesity-associated single-nucleotide polymorphisms have been functionally characterized. Leptin-responsive neurons in the hypothalamus are essential in controlling energy homoeostasis and body weight. Here, we combine fluorescence-activated cell sorting of leptin-responsive hypothalamic neuron nuclei with genomic and epigenomic approaches (RNA sequencing, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin sequencing) to generate a comprehensive map of leptin response-specific regulatory elements, several of which overlap obesity-associated genome-wide association study variants. We demonstrate the usefulness of our leptin response neuron regulome, by functionally characterizing an enhancer near Socs3, a leptin response-associated transcription factor. We envision our data to serve as a useful resource and a blueprint for functionally characterizing obesity-associated single-nucleotide polymorphisms in the hypothalamus.

リンク情報
DOI
https://doi.org/10.1038/s42255-019-0051-x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31535083
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750255
URL
http://europepmc.org/abstract/med/31535083
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85065120609&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85065120609&origin=inward

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