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

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

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Abstract

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
DOIs
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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