title: Maternal Hyperglycemia Disrupts Histone 3 Lysine 36 Trimethylation of the IGF-1 Gene.
abstract: In utero environmental adaptation may predispose to lifelong morbidity. Organisms fine-tune gene expression to achieve environmental adaptation by epigenetic alterations of histone markers of gene accessibility. One example of epigenetics is how uteroplacental insufficiency-induced intrauterine growth restriction (IUGR), which predisposes to adult onset insulin resistance, decreases postnatal IGF-1 mRNA variants and the gene elongation mark histone 3 trimethylation of lysine 36 of the IGF-1 gene (H3Me3K36). Limitations in the study of epigenetics exist due to lack of a primary transgenic epigenetic model. Therefore we examined the epigenetic profile of insulin-like growth factor 1 (IGF-1) in a well-characterized rat model of maternal hyperglycemia to determine if the epigenetic profile of IGF-1 is conserved in disparate models of in utero adaptation. We hypothesized that maternal hyperglycemia would increase IGF-1 mRNA variants and H3Me3K36. However maternal hyperglycemia decreased hepatic IGF-1 mRNA variants and H3Me3K36. This finding is intriguing given that despite different prenatal insults and growth, both maternal hyperglycemia and IUGR predispose to adult onset insulin resistance. We speculate that H3Me3K36 of the IGF-1 gene is sensitive to the glucose level of the prenatal environment, with resultant alteration of IGF-1 mRNA expression and ultimately vulnerability to adult onset insulin resistance.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah, 295 Chipeta Way, Salt Lake City, UT 84108, USA.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Zinkhan
authors.forename: Qi
authors.initials: Q
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Yu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Callaway
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Segar
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Scholz
authors.forename: Robert A
authors.initials: RA
authors.lastname: McKnight
authors.forename: Lisa
authors.initials: L
authors.lastname: Joss-Moore
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lane