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

Autor: 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.
Zdroj: Autophagy; Jan2019, Vol. 15 Issue 1, p98-112, 15p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index