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Your search keyword '"Kathleen M Hudson"' showing total 2 results
Start Over Author "Kathleen M Hudson" Topic dna methylation
2 results on '"Kathleen M Hudson"'

1. Epigenetic control of the imprinted growth regulator Cdkn1c in cadmium-induced placental dysfunction

Author

Mark D. Simmers, Kathleen M. Hudson, Marine Baptissart, and Michael Cowley

Subjects
genomic imprinting, imprinted genes, dna methylation, placenta, cadmium, foetal growth restriction, cdkn1c, toxic metal, Genetics, QH426-470
Abstract

Cadmium (Cd) is a toxic metal ubiquitous in the environment. In utero, Cd is inefficiently transported to the foetus but causes foetal growth restriction (FGR), likely through impairment of the placenta where Cd accumulates. However, the underlying molecular mechanisms are poorly understood. Cd can modulate the expression of imprinted genes, defined by their transcription from one parental allele, which play critical roles in placental and foetal growth. The expression of imprinted genes is governed by DNA methylation at Imprinting Control Regions (ICRs), which are susceptible to environmental perturbation. The imprinted gene Cdkn1c/CDKN1C is a major regulator of placental development, is implicated in FGR, and shows increased expression in response to Cd exposure in mice. Here, we use a hybrid mouse model of in utero Cd exposure to determine if the increase in placental Cdkn1c expression is caused by changes to ICR DNA methylation and loss of imprinting (LOI). Consistent with prior studies, Cd causes FGR and impacts placental structure and Cdkn1c expression at late gestation. Using polymorphisms to distinguish parental alleles, we demonstrate that increased Cdkn1c expression is not driven by changes to DNA methylation or LOI. We show that Cdkn1c is expressed primarily in the placental labyrinth which is proportionally increased in size in response to Cd. We conclude that the Cd-associated increase in Cdkn1c expression can be fully explained by alterations to placental structure. These results have implications for understanding mechanisms of Cd-induced placental dysfunction and, more broadly, for the study of FGR associated with increased Cdkn1c/CDKN1C expression.

Published
2022
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2. Effects of Cadmium Exposure on DNA Methylation at Imprinting Control Regions and Genome-Wide in Mothers and Newborn Children

Author

Dereje D. Jima, David Skaar, Sarah S Park, Rachel L. Maguire, Cathrine Hoyo, Patricia Sorrow, Michael Cowley, and Kathleen M Hudson

Subjects
0301 basic medicine, Male, Health, Toxicology and Mutagenesis, Mothers, Biology, Genome, Epigenesis, Genetic, 03 medical and health sciences, Genomic Imprinting, Gene expression, Humans, Allele, Imprinting (psychology), Epigenesis, 2. Zero hunger, Genetics, Research, Public Health, Environmental and Occupational Health, Infant, Newborn, DNA Methylation, CADMIUM EXPOSURE, 030104 developmental biology, DNA methylation, Female, Genomic imprinting, Cadmium
Abstract

Background: Imprinted genes are defined by their preferential expression from one of the two parental alleles. This unique mode of gene expression is dependent on allele-specific DNA methylation profiles established at regulatory sequences called imprinting control regions (ICRs). These loci have been used as biosensors to study how environmental exposures affect methylation and transcription. However, a critical unanswered question is whether they are more, less, or equally sensitive to environmental stressors as the rest of the genome. Objectives: Using cadmium exposure in humans as a model, we aimed to determine the relative sensitivity of ICRs to perturbation of methylation compared to similar, nonimprinted loci in the genome. Methods: We assayed DNA methylation genome-wide using bisulfite sequencing of 19 newborn cord blood and 20 maternal blood samples selected on the basis of maternal blood cadmium levels. Differentially methylated regions (DMRs) associated with cadmium exposure were identified. Results: In newborn cord blood and maternal blood, 641 and 1,945 cadmium-associated DMRs were identified, respectively. DMRs were more common at the 15 maternally methylated ICRs than at similar nonimprinted loci in newborn cord blood (p=5.64×10−8) and maternal blood (p=6.22×10−14), suggesting a higher sensitivity for ICRs to cadmium. Genome-wide, Enrichr analysis indicated that the top three functional categories for genes that overlapped DMRs in maternal blood were body mass index (BMI) (p=2.0×10−5), blood pressure (p=3.8×10−5), and body weight (p=0.0014). In newborn cord blood, the top three functional categories were BMI, atrial fibrillation, and hypertension, although associations were not significant after correction for multiple testing (p=0.098). These findings suggest that epigenetic changes may contribute to the etiology of cadmium-associated diseases. Conclusions: We analyzed cord blood and maternal blood DNA methylation profiles genome-wide at nucleotide resolution in individuals selected for high and low blood cadmium levels in the first trimester. Our findings suggest that ICRs may be hot spots for perturbation by cadmium, motivating further study of these loci to investigate potential mechanisms of cadmium action. https://doi.org/10.1289/EHP2085

Published
2017

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