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

Autophagy
J G C PeetersJ van Loosdregt

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.

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Citations

Aug 4, 2020·Human Molecular Genetics·Ata AbbasCharis Eng
May 31, 2019·Human Genetics·Shi Q WongLouis R Lapierre
Jul 25, 2019·Frontiers in Immunology·Anna Elisa Andrea Surace, Christian M Hedrich
Jan 10, 2021·The International Journal of Biochemistry & Cell Biology·Gang YinHaodong Lin
Jul 2, 2021·Frontiers in Cell and Developmental Biology·Yin ShiNancy Gordon
Jul 7, 2021·Cellular and Molecular Life Sciences : CMLS·Eva-Maria EcklLucas T Jae
Aug 27, 2021·Frontiers in Cell and Developmental Biology·Bei YinLing Ye
Nov 4, 2021·Cell Death & Disease·Matteo BordiFrancesco Cecconi

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Datasets Mentioned

BETA
GSM803414
and
GSM803434
GSE107603
GSE107600
GSE107599

Methods Mentioned

BETA
acetylation
immunoprecipitation
ChIP-seq
histone acetylation
transfection
RNA-Seq
ChIP
PCR

Software Mentioned

GraphPad Prism
GraphPad
HTSeq
AddOrReplaceReadGroups
edgeR
DESeq2
STAR
Picard
MEME Suite
DESeq

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