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

Autor: Fulvio Reggiori, Mario Mauthe, Janneke G. C. Peeters, J van Loosdregt, E Mocholi, Stephin J. Vervoort, Michal Mokry, C. de Heus, SJ Vastert, S G J M Coenen, L W Picavet, Judith Klumperman, P. J. Coffer
Přispěvatelé: Microbes in Health and Disease (MHD), Center for Liver, Digestive and Metabolic Diseases (CLDM)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Autophagy
Autophagy, 15(1), 98. Landes Bioscience
Autophagy, 15(1), 98-112. Taylor & Francis Group
ISSN: 1554-8635
1554-8627
Popis: 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.
Databáze: OpenAIRE