Epigenetic regulation of maspin expression in the human placenta.
Maspin, a tumour suppressor gene, is differentially expressed in the human placenta. Decreased expression of maspin in the first trimester corresponds with the period of maximum trophoblast invasion, suggesting a role in cell invasion and motility. Although methylation of CpG islands regulates maspin expression in cancer cells, the mechanism of maspin regulation in the human placenta is unknown. Our objectives were to determine the role of epigenetic alterations in the regulation of maspin expression in the placenta. Placental samples obtained from 7 to 40 weeks' gestation were used for bisulphite sequencing and chromatin immunoprecipitation (ChIP) PCR. There was no significant change in the methylation indices in the promoter region of maspin throughout gestation. The levels of histone modifications associated with transcriptionally active chromatin were significantly different in placental tissues from second and third trimester relative to those from first trimester. Addition of trichostatin A (TSA) to placental explants increased the maspin mRNA expression (8- to 20-fold), whereas addition of 5-aza-cytidine (5-AzaC) had no effect on maspin expression. Our data suggest that maspin expression in the human placenta is regulated by changes in histone tail modifications. This is the first report of selective histone modifications associated with differential placental gene expression in human gestation.
Dokras
Anuja
A
Department of Obstetrics and Gynecology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.
Coffin
Jeremy
J
Field
Lorie
L
Frakes
Amanda
A
Lee
Hwahyung
H
Madan
Anuradha
A
Nelson
Timothy
T
Ryu
Gi-Yung
GY
Yoon
Jae-Geun
JG
Madan
Anup
A
D000107:Acetylation; D001374:Azacitidine / Q000494:pharmacology; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D005865:Gestational Age; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015843:Serpins / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C085344:SERPIN-B5; D015843:Serpins; C012589:trichostatin A; D006655:Histone Deacetylases; D001374:Azacitidine