title: Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation.
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.
authors.affiliation: Department of Medicine, University of Washington, 850 Republican St., Rm 242, Seattle, WA 98109, USA. Electronic address: odenis@uw.edu.
authors.forename: Oleg
authors.initials: O
authors.lastname: Denisenko
authors.affiliation: Centre for Biological Sciences, University of Southampton, Mailpoint 840, Level D Lab & Path Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
authors.forename: Emma S
authors.initials: ES
authors.lastname: Lucas
authors.affiliation: Centre for Biological Sciences, University of Southampton, Mailpoint 840, Level D Lab & Path Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
authors.forename: Congshan
authors.initials: C
authors.lastname: Sun
authors.affiliation: Centre for Biological Sciences, University of Southampton, Mailpoint 840, Level D Lab & Path Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Watkins
authors.affiliation: Department of Medicine, University of Washington, 850 Republican St., Rm 242, Seattle, WA 98109, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mar
authors.affiliation: Department of Medicine, University of Washington, 850 Republican St., Rm 242, Seattle, WA 98109, USA.
authors.forename: Karol
authors.initials: K
authors.lastname: Bomsztyk
authors.affiliation: Centre for Biological Sciences, University of Southampton, Mailpoint 840, Level D Lab & Path Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
authors.forename: Tom P
authors.initials: TP
authors.lastname: Fleming
mesh_terms: D000818:Animals; D004032:Diet; D010064:Embryo Implantation / Q000235:genetics*; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000235:genetics*; D012335:RNA, Ribosomal / Q000235:genetics*
chemical_list: D012335:RNA, Ribosomal
keywords: DNA methylation; Maternal diet; RRN3; TIF-1A; Thrifty gene; rDNA transcription