Inhibitors of histone deacetylases and DNA methyltransferases alter imprinted gene regulation in embryonic stem cells

Senan Baqir, Lawrence C. Smith

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Pluripotent embryonic stem cells are able to differentiate into a variety of cell types, thereby making them a valuable source for transplantation medicine. Recent studies have reported the use of pharmacological agents, namely 5-Aza-Cytidine (5AzaC) and Trichostatin A (TSA), to guide embryonic stem (ES) cells to differentiate into specific cellular lineages. However, those drugs are known to be potent inhibitors of DNA methyltransferases and/or histone deacetylases. Since both epigenetic mechanisms are involved in the expression of imprinted genes in fetal and adult somatic tissues, it is essential to investigate further the role of these agents in regulating imprinted gene expression in embryonic cells. Embryonic stem cells were exposed to 5AzaC and TSA and analyzed for transcript abundance of a number of imprinted and non-imprinted marker genes. Most imprinted gene transcripts increased following exposure to 5AzaC or TSA alone and responded in either an additive or synergistic manner when exposed to both drugs together. Interestingly, transcript levels of several imprinted genes remained high and in some cases, increased further after drug removal or even after passageing the cells, indicating a long lasting and retarded effect on gene expression. Together, our results suggest that DNA methylation and histone acetylation play jointly an important epigenetic role in governing imprinted gene expression in embryonic stem cells. Moreover, these results describe the sensitivity and irreversibility of embryonic stem cells to epigenetic modifiers, highlighting potential risks for their use in therapeutic applications.

Original languageEnglish
Pages (from-to)200-213
Number of pages14
JournalCloning and Stem Cells
Volume8
Issue number3
DOIs
Publication statusPublished - 2006

Fingerprint

Histone Deacetylases
Methyltransferases
Embryonic Stem Cells
trichostatin A
Cytidine
Epigenomics
DNA
Gene Expression
Genes
Pharmaceutical Preparations
Pluripotent Stem Cells
Therapeutic Uses
DNA Methylation
Acetylation
Histones
Transplantation
Medicine
Pharmacology

ASJC Scopus subject areas

  • Biotechnology
  • Developmental Biology
  • Applied Microbiology and Biotechnology

Cite this

Inhibitors of histone deacetylases and DNA methyltransferases alter imprinted gene regulation in embryonic stem cells. / Baqir, Senan; Smith, Lawrence C.

In: Cloning and Stem Cells, Vol. 8, No. 3, 2006, p. 200-213.

Research output: Contribution to journalArticle

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