Publication

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

Peeters, J. G. C., Picavet, L. W., Coenen, S. G. J. M., Mauthe, M., Vervoort, S. J., Mocholi, E., de Heus, C., Klumperman, J., Vastert, S. J., Reggiori, F., Coffer, P. J., Mokry, M. & van Loosdregt, J., 2-Jan-2019, In : Autophagy. 15, 1, p. 98-112 15 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • J G C Peeters
  • L W Picavet
  • S G J M Coenen
  • M Mauthe
  • S J Vervoort
  • E Mocholi
  • C de Heus
  • J Klumperman
  • S J Vastert
  • F Reggiori
  • P J Coffer
  • M Mokry
  • J van Loosdregt

Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation.

Original languageEnglish
Pages (from-to)98-112
Number of pages15
JournalAutophagy
Volume15
Issue number1
Early online date28-Aug-2018
Publication statusPublished - 2-Jan-2019

    Keywords

  • Autophagy, ChIP-seq, EGR1, nutrient-deprivation, RNA-seq, NF-KAPPA-B, DOWN-REGULATION, HISTONE H4, ACTIVATION, EXPRESSION, ACETYLATION, PATHWAY, RESISTANCE, ENHANCERS

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