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BioMed Research International
Volume 2015 (2015), Article ID 202914, 13 pages
Research Article

Epigenomics of Neural Cells: REST-Induced Down- and Upregulation of Gene Expression in a Two-Clone PC12 Cell Model

1Scientific Institute San Raffaele, Center for Translational Genomics and Bioinformatics, 20132 Milan, Italy
2CNR Institute of Neuroscience, 20129 Milan, Italy
3Humanitas Research Center, Rozzano, 20089 Milan, Italy
4Boehringer Ingelheim, 88400 Biberach an der Riß, Germany
5Division of Neurosciences, San Raffaele Institute and Vita-Salute San Raffaele University, 20133 Milan, Italy

Received 16 March 2015; Accepted 16 July 2015

Academic Editor: Salvatore Spicuglia

Copyright © 2015 Jose M. Garcia-Manteiga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Cell epigenomics depends on the marks released by transcription factors operating via the assembly of complexes that induce focal changes of DNA and histone structure. Among these factors is REST, a repressor that, via its strong decrease, governs both neuronal and neural cell differentiation and specificity. REST operation on thousands of possible genes can occur directly or via indirect mechanisms including repression of other factors. In previous studies of gene down- and upregulation, processes had been only partially investigated in neural cells. PC12 are well-known neural cells sharing properties with neurons. In the widely used PC12 populations, low-REST cells coexist with few, spontaneous high-REST PC12 cells. High- and low-REST PC12 clones were employed to investigate the role and the mechanisms of the repressor action. Among 15,500 expressed genes we identified 1,770 target and nontarget, REST-dependent genes. Functionally, these genes were found to operate in many pathways, from synaptic function to extracellular matrix. Mechanistically, downregulated genes were predominantly repressed directly by REST; upregulated genes were mostly governed indirectly. Among other factors, Polycomb complexes cooperated with REST for downregulation, and Smad3 and Myod1 participated in upregulation. In conclusion, we have highlighted that PC12 clones are a useful model to investigate REST, opening opportunities to development of epigenomic investigation.