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

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