Epigenetic analysis of human embryonic carcinoma cells during retinoic acid-induced neural differentiation

Maryam Shahhoseini*, Adeleh Taei, Narges Zare Mehrjardi, Ghasem Hosseini Salekdeh, Hossein Baharvand

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Differentiation of stem cells from a pluripotent to a committed state involves global changes in genome expression patterns, critically determined by chromatin structure and interactions of chromatin-binding proteins. The dynamics of chromatin structure are tightly regulated by multiple epigenetic mechanisms such as histone modifications and the incorporation of histone variants. In the current work, we induced neural differentiation of a human embryonal carcinoma stem cell line, NTERA2/NT2, by retinoic acid (RA) treatment, primarily according to two different methods of adherent cell culture (rosette formation) and suspension cell culture (EB formation) conditions, and histone modifications and variations were compared through these processes. Western blot analysis of histone extracts showed significant changes in the acetylation and methylation patterns of histone H3, and expression level of the histone variant H2A.Z, after RA treatment in both protocols. Using chromatin immunoprecipitation (ChIP) coupled with real-time PCR, it was shown that these epigenetic changes occurred on the regulatory regions of 4 marker genes (Oct4, Nanog, Nestin, and Pax6) in a culture condition dependent manner. This report demonstrates the dynamic interplay of histone modification and variation in regulating the gene expression profile, during stem cell differentiation and under different culture conditions.

Original languageEnglish
Pages (from-to)527-538
Number of pages12
JournalBiochemistry and Cell Biology
Issue number3
Publication statusPublished - 1 Jun 2010
Externally publishedYes


  • Epigenetic
  • H2A.Z
  • Neural differentiation
  • NTERA2
  • Retinoic acid


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