Epigenetic regulation of autophagy by the methyltransferase G9a

Amaia Artal Martinez De Narvajas, Timothy S. Gomez, Jin San Zhang, Alexander O. Mann, Yoshiyuki Taoda, Jacquelyn A. Gorman, Marta Herreros-Villanueva, Thomas M. Gress, Volker Ellenrieder, Luis Bujand, Do Hyung Kim, Alan P. Kozikowski, Alexander Koenig, Daniel D Billadeau

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the cytoplasmic machinery that orchestrates autophagy induction during starvation, hypoxia, or receptor stimulation has been widely studied, the key epigenetic events that initiate and maintain the autophagy process remain unknown. Here we show that the methyltransferase G9a coordinates the transcriptional activation of key regulators of autophagosome formation by remodeling the chromatin landscape. Pharmacological inhibition or RNA interference (RNAi)-mediated suppression of G9a induces LC3B expression and lipidation that is dependent on RNA synthesis, protein translation, and the methyltransferase activity of G9a. Under normal conditions, G9a associates with the LC3B, WIPI1, and DOR gene promoters, epigenetically repressing them. However, G9a and G9a-repressive histone marks are removed during starvation and receptor-stimulated activation of naive T cells, two physiological inducers of macroautophagy. Moreover, we show that the c-Jun N-terminal kinase (JNK) pathway is involved in the regulation of autophagy gene expression during naive-T-cell activation. Together, these findings reveal that G9a directly represses genes known to participate in the autophagic process and that inhibition of G9a-mediated epigenetic repression represents an important regulatory mechanism during autophagy.

Original languageEnglish (US)
Pages (from-to)3983-3993
Number of pages11
JournalMolecular and Cellular Biology
Volume33
Issue number20
DOIs
StatePublished - 2013

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Autophagy
Methyltransferases
Epigenomics
Starvation
Epigenetic Repression
Histone Code
Protein Methyltransferases
T-Lymphocytes
Chromatin Assembly and Disassembly
JNK Mitogen-Activated Protein Kinases
Gene Expression Regulation
Protein Biosynthesis
RNA Interference
Organelles
Transcriptional Activation
Genes
Pharmacology
RNA
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

De Narvajas, A. A. M., Gomez, T. S., Zhang, J. S., Mann, A. O., Taoda, Y., Gorman, J. A., ... Billadeau, D. D. (2013). Epigenetic regulation of autophagy by the methyltransferase G9a. Molecular and Cellular Biology, 33(20), 3983-3993. https://doi.org/10.1128/MCB.00813-13

Epigenetic regulation of autophagy by the methyltransferase G9a. / De Narvajas, Amaia Artal Martinez; Gomez, Timothy S.; Zhang, Jin San; Mann, Alexander O.; Taoda, Yoshiyuki; Gorman, Jacquelyn A.; Herreros-Villanueva, Marta; Gress, Thomas M.; Ellenrieder, Volker; Bujand, Luis; Kim, Do Hyung; Kozikowski, Alan P.; Koenig, Alexander; Billadeau, Daniel D.

In: Molecular and Cellular Biology, Vol. 33, No. 20, 2013, p. 3983-3993.

Research output: Contribution to journalArticle

De Narvajas, AAM, Gomez, TS, Zhang, JS, Mann, AO, Taoda, Y, Gorman, JA, Herreros-Villanueva, M, Gress, TM, Ellenrieder, V, Bujand, L, Kim, DH, Kozikowski, AP, Koenig, A & Billadeau, DD 2013, 'Epigenetic regulation of autophagy by the methyltransferase G9a', Molecular and Cellular Biology, vol. 33, no. 20, pp. 3983-3993. https://doi.org/10.1128/MCB.00813-13
De Narvajas AAM, Gomez TS, Zhang JS, Mann AO, Taoda Y, Gorman JA et al. Epigenetic regulation of autophagy by the methyltransferase G9a. Molecular and Cellular Biology. 2013;33(20):3983-3993. https://doi.org/10.1128/MCB.00813-13
De Narvajas, Amaia Artal Martinez ; Gomez, Timothy S. ; Zhang, Jin San ; Mann, Alexander O. ; Taoda, Yoshiyuki ; Gorman, Jacquelyn A. ; Herreros-Villanueva, Marta ; Gress, Thomas M. ; Ellenrieder, Volker ; Bujand, Luis ; Kim, Do Hyung ; Kozikowski, Alan P. ; Koenig, Alexander ; Billadeau, Daniel D. / Epigenetic regulation of autophagy by the methyltransferase G9a. In: Molecular and Cellular Biology. 2013 ; Vol. 33, No. 20. pp. 3983-3993.
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