β-actin regulates a heterochromatin landscape essential for optimal induction of neuronal programs during direct reprograming

Xin Xie, Robertas Jankauskas, Aslam M.A. Mazari, Nizar Drou, Piergiorgio Percipalle

    Research output: Contribution to journalArticle

    Abstract

    During neuronal development, β-actin serves an important role in growth cone mediated axon guidance. Consistent with this notion, in vivo ablation of the β-actin gene leads to abnormalities in the nervous system. However, whether β-actin is involved in the regulation of neuronal gene programs is not known. In this study, we directly reprogramed β-actin+/+ WT, β-actin+/- HET and β-actin-/- KO mouse embryonic fibroblast (MEFs) into chemically induced neurons (CiNeurons). Using RNA-seq analysis, we profiled the transcriptome changes among the CiNeurons. We discovered that induction of neuronal gene programs was impaired in KO CiNeurons in comparison to WT ones, whereas HET CiNeurons showed an intermediate levels of induction. ChIP-seq analysis of heterochromatin markers demonstrated that the impaired expression of neuronal gene programs correlated with the elevated H3K9 and H3K27 methylation levels at gene loci in β-actin deficient MEFs, which is linked to the loss of chromatin association of the BAF complex ATPase subunit Brg1. Together, our study shows that heterochromatin alteration in β-actin null MEFs impedes the induction of neuronal gene programs during direct reprograming. These findings are in line with the notion that H3K9Me3-based heterochromatin forms a major epigenetic barrier during cell fate change.

    Original languageEnglish (US)
    Article numbere1007846
    JournalPLoS Genetics
    Volume14
    Issue number12
    DOIs
    StatePublished - Dec 1 2018

    Fingerprint

    Heterochromatin
    heterochromatin
    actin
    Actins
    gene
    neurons
    fibroblasts
    Neurons
    genes
    Fibroblasts
    Genes
    mice
    methylation
    nervous system
    abnormality
    Nervous System Malformations
    ablation
    Growth Cones
    programme
    RNA

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Molecular Biology
    • Genetics
    • Genetics(clinical)
    • Cancer Research

    Cite this

    β-actin regulates a heterochromatin landscape essential for optimal induction of neuronal programs during direct reprograming. / Xie, Xin; Jankauskas, Robertas; Mazari, Aslam M.A.; Drou, Nizar; Percipalle, Piergiorgio.

    In: PLoS Genetics, Vol. 14, No. 12, e1007846, 01.12.2018.

    Research output: Contribution to journalArticle

    Xie, Xin ; Jankauskas, Robertas ; Mazari, Aslam M.A. ; Drou, Nizar ; Percipalle, Piergiorgio. / β-actin regulates a heterochromatin landscape essential for optimal induction of neuronal programs during direct reprograming. In: PLoS Genetics. 2018 ; Vol. 14, No. 12.
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