Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation

Oleg Denisenko, Emma S. Lucas, Congshan Sun, Adam J. Watkins, Daniel Mar, Karol Brmsztyk, Tom P. Fleming

Research output: Contribution to journalArticle

Abstract

Cells and organisms respond to nutrient deprivation by decreasing global rates of transcription, translation and DNA replication. To what extent such changes can be reversed is largely unknown. We examined the effect of maternal dietary restriction on RNA synthesis in the offspring. Low protein diet fed either throughout gestation or for the preimplantation period alone reduced cellular RNA content across fetal somatic tissues during challenge and increased it beyond controls in fetal and adult tissues after challenge release. Changes in transcription of ribosomal RNA, the major component of cellular RNA, were responsible for this phenotype as evidenced by matching alterations in RNA polymerase I density and DNA methylation at ribosomal DNA loci. Cellular levels of the ribosomal transcription factor Rrn3 mirrored the rRNA expression pattern. In cell culture experiments, Rrn3 overexpression reduced rDNA methylation and increased rRNA expression; the converse occurred after inhibition of Rrn3 activity. These observations define novel mechanism where poor nutrition before implantation irreversibly alters basal rates of rRNA transcription thereafter in a process mediated by rDNA methylation and Rrn3 factor.
Original languageEnglish
Pages (from-to)906–913
Number of pages8
JournalBBA Gene Regulatory Mechanisms
Volume1859
Issue number7
Early online date7 Apr 2016
DOIs
Publication statusPublished - Jul 2016

Bibliographical note

© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Funding: BBSRC [BB/I001840/1; BB/F007450/1] and EU FP7-CP-FP EpiHealth programme [278418]

Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.bbagrm.2016.04.001

Keywords

  • rDNA transcription
  • maternal diet
  • DNA methylation
  • RRN3
  • TIF-1A
  • thrifty gene

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