Intrauterine growth restriction affects hippocampal dual specificity phosphatase 5 gene expression and epigenetic characteristics. Physiol Genomics 2011 Oct 20;43(20):1160-9
Date
08/11/2011Pubmed ID
21828247Pubmed Central ID
PMC3217330DOI
10.1152/physiolgenomics.00242.2010Scopus ID
2-s2.0-80054817669 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
Intrauterine growth retardation (IUGR) predisposes humans toward hippocampal morbidities, such as impaired learning and memory. Hippocampal dual specificity phosphatase 5 (DUSP5) may be involved in these morbidities because DUSP5 regulates extracellular signal-regulated kinase phosphorylation (Erk). In the rat, IUGR causes postnatal changes in hippocampal gene expression and epigenetic characteristics. However, the impact of IUGR upon hippocampal DUSP5 expression and epigenetic characteristics is not known. We therefore hypothesized that IUGR affects hippocampal 1) DUSP5 expression, DNA CpG methylation, and histone code, and 2) erk1/2 phosphorylation in a well-characterized rat model of IUGR. We found that IUGR significantly decreased DUSP5 expression in the day of life (DOL) 0 and 21 male rat, while decreasing only DUSP5 protein levels in the DOL21 female rat. Fluorescent in situ hybridization and immunohistochemistry analyses localized the changes in DUSP5 mRNA and protein, many of which occurred in the dentate gyrus. IUGR also caused sex-specific differences in DNA CpG methylation and histone code in two sites of the hippocampal DUSP5 gene, a 5'-flanking specificity protein-1 (SP1) site and exon 2. Finally, when IUGR decreased DUSP5 protein levels, Erk phosphorylation increased. We conclude that IUGR affects hippocampal DUSP5 expression and epigenetic characteristics in a sex-specific manner.
Author List
Ke X, McKnight RA, Caprau D, O'Grady S, Fu Q, Yu X, Callaway CW, Albertine KH, Lane RHMESH terms used to index this publication - Major topics in bold
AnimalsCpG Islands
DNA Methylation
Dual-Specificity Phosphatases
Epigenesis, Genetic
Extracellular Signal-Regulated MAP Kinases
Female
Fetal Growth Retardation
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Hippocampus
Histone Code
Immunohistochemistry
In Situ Hybridization, Fluorescence
Male
Phosphorylation
RNA, Messenger
Rats