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

OnderzoeksoutputAcademicpeer review

23 Citaten (Scopus)
253 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)98-112
Aantal pagina's15
TijdschriftAutophagy
Volume15
Nummer van het tijdschrift1
Vroegere onlinedatum28-aug-2018
DOI's
StatusPublished - 2-jan-2019

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