Epigenetics (Feb 2020)

Human chromatin remodeler cofactor, RNA interactor, eraser and writer sperm RNAs responding to obesity

  • Grace M. Swanson,
  • Molly Estill,
  • Michael P. Diamond,
  • Richard S. Legro,
  • Christos Coutifaris,
  • Kurt T. Barnhart,
  • Hao Huang,
  • Karl R. Hansen,
  • J. C. Trussell,
  • R. Matthew Coward,
  • Heping Zhang,
  • Robert Goodrich,
  • Stephen A. Krawetz

DOI
https://doi.org/10.1080/15592294.2019.1644880
Journal volume & issue
Vol. 15, no. 1-2
pp. 32 – 46

Abstract

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In the United States almost 33% of adults are considered obese (BMI > 30 kg/m2). Both animal models and to a lesser extent human studies, have associated BMI, a measure of obesity, with alterations in sperm DNA methylation and RNAs. Sperm RNAs from the Assessment of Multiple Gestations from Ovarian Stimulation trial, were isolated and sequenced. A Generalized Linear Model identified 487 BMI associated human sperm RNA elements (short exon-sized sequences). They partitioned into four patterns; a continual increase with BMI, increase once obese (BMI>30 kg/m2); a steady decrease with BMI; and decrease once overweight (BMI 25 - 30 kg/m2). Gene Ontology revealed a unique relationship between BMI and transcripts associated with chromosome organization, adipogenesis, cellular stress and obesity-related inflammation. Coregulatory networks linked by Chromatin remodeler cofactors, RNA interactors, Erasers and Writers (CREWs) were uncovered to reveal a hierarchical epigenetic response pathway.

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