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

Jose M. Garcia-Manteiga, Silvia Bonfiglio, Maria Luisa Malosio, Dejan Lazarevic, Elia Stupka, Davide Cittaro, Jacopo Meldolesi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number202914
JournalBioMed Research International
Volume2015
DOIs
Publication statusPublished - 2015

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Clone cells
PC12 Cells
Epigenomics
Gene expression
Up-Regulation
Down-Regulation
Clone Cells
Genes
Gene Expression
Histones
Neurons
Extracellular Matrix
Cell Differentiation
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Epigenomics of Neural Cells : REST-Induced Down- and Upregulation of Gene Expression in a Two-Clone PC12 Cell Model. / Garcia-Manteiga, Jose M.; Bonfiglio, Silvia; Malosio, Maria Luisa; Lazarevic, Dejan; Stupka, Elia; Cittaro, Davide; Meldolesi, Jacopo.

In: BioMed Research International, Vol. 2015, 202914, 2015.

Research output: Contribution to journalArticle

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