Induction of a trophoblast-like phenotype by hydralazine in the p19 embryonic carcinoma cell line

Cliona M. O'Driscoll, Jonathan B. Coulter, Joseph Bressler

Research output: Contribution to journalArticle

Abstract

Chemicals that affect cellular differentiation through epigenetic mechanisms have potential utility in treating a wide range of diseases. Hydralazine decreases DNA methylation in some cell types but its effect on differentiation has not been well explored. After five days of exposure to hydralazine, P19 embryocarcinoma cells displayed a giant cell morphology and were binucleate, indicative of a trophoblast-like morphology. Other trophoblast-like properties included the intermediary filament Troma-1/cytokeratin 8 and the transcription factor Tead4. A decrease in CpG methylation at three sites in the TEAD4 promoter and the B1 repeated sequence was observed. Knocking down expression of Tead4 with siRNA blocked the increase in Troma-1/cytokeratin 8 and over expression of Tead4 induced the expression of Troma-1/cytokeratin 8. Cells treated for 5. days with hydralazine were no longer capable of undergoing retinoic acid-mediated neuronal differentiation. An irreversible loss of the pluripotent transcription factor Oct-4 was observed following hydralazine exposure. In summary, hydralazine induces P19 cells to assume a trophoblast-like phenotype by upregulating Tead4 expression through a mechanism involving DNA demethylation.

Original languageEnglish (US)
Pages (from-to)460-467
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

Hydralazine
Trophoblasts
Keratin-8
Carcinoma
Phenotype
Cell Line
Octamer Transcription Factor-3
DNA Methylation
Giant Cells
Tretinoin
Epigenomics
Methylation
Small Interfering RNA
Transcription Factors
DNA

Keywords

  • DNA methylation
  • Hydralazine
  • P19 cell
  • Tead4
  • Trophoblast

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Induction of a trophoblast-like phenotype by hydralazine in the p19 embryonic carcinoma cell line. / O'Driscoll, Cliona M.; Coulter, Jonathan B.; Bressler, Joseph.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1833, No. 3, 03.2013, p. 460-467.

Research output: Contribution to journalArticle

@article{81e2f28b6049408b812ecffea8656965,
title = "Induction of a trophoblast-like phenotype by hydralazine in the p19 embryonic carcinoma cell line",
abstract = "Chemicals that affect cellular differentiation through epigenetic mechanisms have potential utility in treating a wide range of diseases. Hydralazine decreases DNA methylation in some cell types but its effect on differentiation has not been well explored. After five days of exposure to hydralazine, P19 embryocarcinoma cells displayed a giant cell morphology and were binucleate, indicative of a trophoblast-like morphology. Other trophoblast-like properties included the intermediary filament Troma-1/cytokeratin 8 and the transcription factor Tead4. A decrease in CpG methylation at three sites in the TEAD4 promoter and the B1 repeated sequence was observed. Knocking down expression of Tead4 with siRNA blocked the increase in Troma-1/cytokeratin 8 and over expression of Tead4 induced the expression of Troma-1/cytokeratin 8. Cells treated for 5. days with hydralazine were no longer capable of undergoing retinoic acid-mediated neuronal differentiation. An irreversible loss of the pluripotent transcription factor Oct-4 was observed following hydralazine exposure. In summary, hydralazine induces P19 cells to assume a trophoblast-like phenotype by upregulating Tead4 expression through a mechanism involving DNA demethylation.",
keywords = "DNA methylation, Hydralazine, P19 cell, Tead4, Trophoblast",
author = "O'Driscoll, {Cliona M.} and Coulter, {Jonathan B.} and Joseph Bressler",
year = "2013",
month = "3",
doi = "10.1016/j.bbamcr.2012.11.012",
language = "English (US)",
volume = "1833",
pages = "460--467",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Induction of a trophoblast-like phenotype by hydralazine in the p19 embryonic carcinoma cell line

AU - O'Driscoll, Cliona M.

AU - Coulter, Jonathan B.

AU - Bressler, Joseph

PY - 2013/3

Y1 - 2013/3

N2 - Chemicals that affect cellular differentiation through epigenetic mechanisms have potential utility in treating a wide range of diseases. Hydralazine decreases DNA methylation in some cell types but its effect on differentiation has not been well explored. After five days of exposure to hydralazine, P19 embryocarcinoma cells displayed a giant cell morphology and were binucleate, indicative of a trophoblast-like morphology. Other trophoblast-like properties included the intermediary filament Troma-1/cytokeratin 8 and the transcription factor Tead4. A decrease in CpG methylation at three sites in the TEAD4 promoter and the B1 repeated sequence was observed. Knocking down expression of Tead4 with siRNA blocked the increase in Troma-1/cytokeratin 8 and over expression of Tead4 induced the expression of Troma-1/cytokeratin 8. Cells treated for 5. days with hydralazine were no longer capable of undergoing retinoic acid-mediated neuronal differentiation. An irreversible loss of the pluripotent transcription factor Oct-4 was observed following hydralazine exposure. In summary, hydralazine induces P19 cells to assume a trophoblast-like phenotype by upregulating Tead4 expression through a mechanism involving DNA demethylation.

AB - Chemicals that affect cellular differentiation through epigenetic mechanisms have potential utility in treating a wide range of diseases. Hydralazine decreases DNA methylation in some cell types but its effect on differentiation has not been well explored. After five days of exposure to hydralazine, P19 embryocarcinoma cells displayed a giant cell morphology and were binucleate, indicative of a trophoblast-like morphology. Other trophoblast-like properties included the intermediary filament Troma-1/cytokeratin 8 and the transcription factor Tead4. A decrease in CpG methylation at three sites in the TEAD4 promoter and the B1 repeated sequence was observed. Knocking down expression of Tead4 with siRNA blocked the increase in Troma-1/cytokeratin 8 and over expression of Tead4 induced the expression of Troma-1/cytokeratin 8. Cells treated for 5. days with hydralazine were no longer capable of undergoing retinoic acid-mediated neuronal differentiation. An irreversible loss of the pluripotent transcription factor Oct-4 was observed following hydralazine exposure. In summary, hydralazine induces P19 cells to assume a trophoblast-like phenotype by upregulating Tead4 expression through a mechanism involving DNA demethylation.

KW - DNA methylation

KW - Hydralazine

KW - P19 cell

KW - Tead4

KW - Trophoblast

UR - http://www.scopus.com/inward/record.url?scp=84871889634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871889634&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2012.11.012

DO - 10.1016/j.bbamcr.2012.11.012

M3 - Article

C2 - 23195226

AN - SCOPUS:84871889634

VL - 1833

SP - 460

EP - 467

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

SN - 0167-4889

IS - 3

ER -