Alterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes.

TitleAlterations to DNA methylation and expression of CXCL14 are associated with suboptimal birth outcomes.
Publication TypeJournal Article
Year of Publication2014
AuthorsCheong CY, Chng K, Lim MKee, Amrithraj AI, Joseph R, Sukarieh R, Tan YChee, Chan L, Tan JHao, Chen L, Pan H, Holbrook JD, Meaney MJ, Chong YSeng, Gluckman PD, Stünkel W
JournalJ Hum Genet
Volume59
Issue9
Pagination504-11
Date Published2014 Sep
ISSN1435-232X
KeywordsAdult, Animals, Caloric Restriction, Cells, Cultured, Chemokines, CXC, CpG Islands, DNA Methylation, Female, Gene Expression Profiling, Humans, Infant, Low Birth Weight, Infant, Newborn, Macaca fascicularis, Male, Maternal Age, Mesenchymal Stromal Cells, Pregnancy, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Umbilical Cord
Abstract

CXCL14 is a chemokine that has previously been implicated in insulin resistance in mice. In humans, the role of CXCL14 in metabolic processes is not well established, and we sought to determine whether CXCL14 is a risk susceptibility gene important in fetal programming of metabolic disease. For this purpose, we investigated whether CXCL14 is differentially regulated in human umbilical cords of infants with varying birth weights. We found an elevated expression of CXCL14 in human low birth weight (LBW) cords, as well as in cords from nutritionally restricted Macaca fascicularis macaques. To further analyze the regulatory mechanisms underlying the expression of CXCL14, we examined CXCL14 in umbilical cord-derived mesenchymal stem cells (MSCs) that provide an in vitro cell-based system amenable to experimental manipulation. Using both whole frozen cords and MSCs, we determined that site-specific CpG methylation in the CXCL14 promoter is associated with altered expression, and that changes in methylation are evident in LBW infant-derived umbilical cords that may indicate future metabolic compromise through CXCL14.

DOI10.1038/jhg.2014.63
Alternate JournalJ. Hum. Genet.
PubMed ID25102097