Genome wide anaylsis of transcriptome modifications in rats exposed to endocrine disruptors. [RNA-Seq]

Our early life environment has a profound influence on developing organs and tissues that impacts metabolic function, and determines health and disease susceptibility across the life-course. We show an adverse early-life exposure that causes metabolic dysfunction in adulthood reprograms active and repressive histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature at specific genes and chromatin states. This epigenomic reprogramming persists long after the initial exposure, but remarkably, can remain transcriptionally- and metabolically-silent until later-life exposure to a Western-style (high fat-fructose-cholesterol) diet. These findings reveal the importance of epigenome:environment interactions across the life-course, which early in life accelerate epigenomic aging and reprogram the epigenome, and later in adulthood, can unlock metabolically restriced epigenetic reprogramming to drive metabolic dysfunction. Overall design: Examination of transcriptomics via RNA-Seq in liver samples from adult (D70) rats on normal chow and adult (D240) rats on Western style diet exposed orally to vehicle or bisphenol A on post-natal days 1, 3, and 5.