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Mol. Hum. Reprod. Advance Access published online on August 26, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal074
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received June 26, 2006
Accepted July 24, 2006

Article

Epigenetic regulation of maspin expression in the human placenta

Anuja Dokras 1, Jeremy Coffin 1, Lorie Field 2, Amanda Frakes 2, Hwahyung Lee 2, Anuradha Madan 2, Timothy Nelson 2, Gi-Yung Ryu 2, Jae-Geun Yoon 2, and Anup Madan 3 *

1 Department of Obstetrics and Gynecology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA
2 Department of Neurosurgery, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA
3 Department of Neurosurgery, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA; Institute for Systems Biology, Seattle, WA, USA

* To whom correspondence should be addressed.
Anup Madan, E-mail: anup-madan{at}uiowa.edu


  Abstract

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.

Keywords: epigenetic regulation/histone modifications/maspin/placenta/promoter methylation.
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