Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment

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PLoS ONE. 2012, 7(5), e36708. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0036708
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Epigenetic changes, including histone modifications or chromatin remodeling are regulated by a large number of human genes. We developed a strategy to study the coordinate regulation of such genes, and to compare different cell populations or tissues. A set of 150 genes, comprising different classes of epigenetic modifiers was compiled. This new tool was used initially to characterize changes during the differentiation of human embryonic stem cells (hESC) to central nervous system neuroectoderm progenitors (NEP). qPCR analysis showed that more than 60% of the examined transcripts were regulated, and .10% of them had a .5-fold increased expression. For comparison, we differentiated hESC to neural crest progenitors (NCP), a distinct peripheral nervous system progenitor population. Some epigenetic modifiers were regulated into the same direction in NEP and NCP, but also distinct differences were observed. For instance, the remodeling ATPase SMARCA2 was up-regulated .30-fold in NCP, while it remained unchanged in NEP; up-regulation of the ATP-dependent chromatin remodeler CHD7 was increased in NEP, while it was down-regulated in NCP. To compare the neural precursor profiles with those of mature neurons, we analyzed the epigenetic modifiers in human cortical tissue. This resulted in the identification of 30 regulations shared between all cell types, such as the histone methyltransferase SETD7. We also identified new markers for post-mitotic neurons, like the arginine methyl transferase PRMT8 and the methyl transferase EZH1. Our findings suggest a hitherto unexpected extent of regulation, and a cell type-dependent specificity of epigenetic modifiers in neurodifferentiation.

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ISO 690WENG, Matthias K., Bastian ZIMMER, Dominik PÖLTL, Marc BROEG, Violeta IVANOVA-ROHLING, John GASPAR, Agapios SACHINIDIS, Ullrich WÜLLNER, Tanja WALDMANN, Marcel LEIST, 2012. Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment. In: PLoS ONE. 2012, 7(5), e36708. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0036708
BibTex
@article{Weng2012Exten-20156,
  year={2012},
  doi={10.1371/journal.pone.0036708},
  title={Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment},
  number={5},
  volume={7},
  journal={PLoS ONE},
  author={Weng, Matthias K. and Zimmer, Bastian and Pöltl, Dominik and Broeg, Marc and Ivanova-Rohling, Violeta and Gaspar, John and Sachinidis, Agapios and Wüllner, Ullrich and Waldmann, Tanja and Leist, Marcel},
  note={Article Number: e36708}
}
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