TY - JOUR
T1 - DNA Methylation Variability in a Single Locus of the RXRα Promoter from Umbilical Vein Blood at Term Pregnancy
AU - Chávez-Lizárraga, Diana
AU - Zárate-Segura, Paola
AU - Beltrán-Montoya, Jorge
AU - Canchola-Sotelo, Carmen
AU - Vadillo-Ortega, Felipe
AU - Chavira-Suárez, Erika
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - DNA methylation status of RXRα gene promoter has been correlated with maternal diet during early pregnancy, and associated with offspring’s adiposity and bone mineral content. In adult life, increased methylation of RXRα promoter region is associated with myocardium pathologies. Early growth response proteins (EGR) are zinc finger transcription factors associated with several cellular pathways such as inflammation, apoptosis, and cardiopathies. DNA-binding sequences of EGR proteins have been reported in the RXRα gene promoter using chromatin immunoprecipitation methods. Here, we used correlations between the maternal pre-pregnancy body mass index (p-BMI), gestational weight gain (GWG), and birth weight (BW) as indirect indicators of the maternal nutritional status as modifier of DNA methylation in the offspring. DNA methylation status from newborns’ umbilical vein blood in full-term pregnancy was evaluated in a short sequence (116 pb) of the RXRα gene promoter that contains the elements of response sequence for EGR proteins. Fifty-three bisulfite-modified DNA samples were assessed through methyl-sensitive high-resolution melting (MS-HRM) analysis. To validate the results, we directly sequenced MS-HRM samples to confirm the presence of CpG-methylated positions. In addition, the RXRα protein levels in extracts of umbilical vein blood were evaluated by western blot. We found differential methylation in a specific locus of the RXRα promoter surrounding the EGR-binding sequence; however, no correlation was found with the level of RXRα protein expression. Variability in the methylation status of the RXRα promoter near the EGR transcription factor binding site in newborn cord blood provides controversial epigenetic insights into RXRα regulation via EGR proteins.
AB - DNA methylation status of RXRα gene promoter has been correlated with maternal diet during early pregnancy, and associated with offspring’s adiposity and bone mineral content. In adult life, increased methylation of RXRα promoter region is associated with myocardium pathologies. Early growth response proteins (EGR) are zinc finger transcription factors associated with several cellular pathways such as inflammation, apoptosis, and cardiopathies. DNA-binding sequences of EGR proteins have been reported in the RXRα gene promoter using chromatin immunoprecipitation methods. Here, we used correlations between the maternal pre-pregnancy body mass index (p-BMI), gestational weight gain (GWG), and birth weight (BW) as indirect indicators of the maternal nutritional status as modifier of DNA methylation in the offspring. DNA methylation status from newborns’ umbilical vein blood in full-term pregnancy was evaluated in a short sequence (116 pb) of the RXRα gene promoter that contains the elements of response sequence for EGR proteins. Fifty-three bisulfite-modified DNA samples were assessed through methyl-sensitive high-resolution melting (MS-HRM) analysis. To validate the results, we directly sequenced MS-HRM samples to confirm the presence of CpG-methylated positions. In addition, the RXRα protein levels in extracts of umbilical vein blood were evaluated by western blot. We found differential methylation in a specific locus of the RXRα promoter surrounding the EGR-binding sequence; however, no correlation was found with the level of RXRα protein expression. Variability in the methylation status of the RXRα promoter near the EGR transcription factor binding site in newborn cord blood provides controversial epigenetic insights into RXRα regulation via EGR proteins.
KW - DNA methylation
KW - EGR transcription factor
KW - MS-HRM
KW - RXRα
KW - Term pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85040032702&partnerID=8YFLogxK
U2 - 10.1007/s10528-017-9838-1
DO - 10.1007/s10528-017-9838-1
M3 - Artículo
C2 - 29305749
SN - 0006-2928
VL - 56
SP - 210
EP - 224
JO - Biochemical Genetics
JF - Biochemical Genetics
IS - 3
ER -