Combination of promoter hypomethylation and PDX1 overexpression leads to TBX15 decrease in vascular IUGR placentas.
Preeclampsia (PE) and vascular intra-uterine growth restriction (vIUGR) are two pathological obstetrical conditions originating from placental dysfunction. Recently, methylation changes at the placental level have been shown to be indicative of these diseases. The alteration of such epigenetic marks is therefore a novel pathway that might be critical for these pathologies. Here, we identified a region located in the distal promoter of the T-box-containing transcription factor TBX15 that is differentially methylated in pathological placentas. The level of methylation correlated significantly with the weight and stature of the newborn. The promoter was found to be hypomethylated in vIUGR coinciding with the down-regulation of its expression. PDX1, a transcription factor important for the regulation of insulin metabolism regulation was able to repress the TBX15 promoter in a methylation-dependent manner, which might, at least partially, explain the specific mRNA decrease of TBX15 observed in vIUGR placentas. Overall, the data presented herein suggest that TBX15 might be involved in the pathophysiology of placental diseases.
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
Sonia T
ST
Chelbi
Ludivine
L
Doridot
Françoise
F
Mondon
Chloé
C
Dussour
Régis
R
Rebourcet
Florence
F
Busato
Géraldine
G
Gascoin-Lachambre
Sandrine
S
Barbaux
Virginie
V
Rigourd
Thérèse-Marie
TM
Mignot
Jörg
J
Tost
Daniel
D
Vaiman
D000328:Adult; D001483:Base Sequence; D002460:Cell Line; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism; D010922:Placenta Diseases / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
D018398:Homeodomain Proteins; D020825:T-Box Domain Proteins; C523795:TBX15 protein, human; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein