Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation.
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.
['Denisenko|Oleg|O|', 'Lucas|Emma S|ES|', 'Sun|Congshan|C|', 'Watkins|Adam J|AJ|', 'Mar|Daniel|D|', 'Bomsztyk|Karol|K|', 'Fleming|Tom P|TP|']
D000818:Animals D004032:Diet D010064:Embryo Implantation D004622:Embryo, Mammalian D047108:Embryonic Development 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 D012335:RNA, Ribosomal
Maternal diet DNA methylation RRN3 TIF-1A Thrifty gene rDNA transcription