Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy
Open accessAbstract
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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The autophagy core list was used for gene set enrichment analysis on published RNA-seq datasets from starved cells or Down syndrome primary fibroblasts.
“Further, we used the “autophagy core” list for gene set enrichment analysis by means of the published RNA-sequencing (RNA-seq) dataset, performed on starved cells [31] or on Down syndrome primary fibroblasts, in which it has been reported an mTORC1 hyperactivation associated to inhibition of autophagy induction [27], and thus demonstrating its effective applicability.”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [31]
Gene set enrichment analyses were performed according to standard procedures on two published RNA-seq datasets.
“Gene set enrichment analyses were performed according to standard procedures [39, 40] on two published RNA-seq datasets [31, 48]”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [31]
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Cites
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TFEB Links Autophagy to Lysosomal Biogenesis
Settembre, C., Di Malta, C., Polito, V. A., Arencibia, M. G., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Medina, D., Colella, P., et al. (2011) · Science · doi:10.1126/science.1204592 · Cited by 3,365 · see citing works
Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Scherz‐Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., & Elazar, Z. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601623 · Cited by 2,101 · cited 1× · see citing works
“Reactive oxygen species (ROS), which can be induced by EBSS treatment, are a known inducer of autophagy [45].”
BackgroundRegulation of autophagy by cytoplasmic p53
Tasdemir, E., Maiuri, M. C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1730 · Cited by 1,132 · see citing works
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Cited by
Sorted by citations
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationA gene toolbox for monitoring autophagy transcription
Bordi, M., De Cegli, R., Testa, B., Nixon, R. A., Ballabio, A., & Cecconi, F. (2021) · Cell Death & Disease · doi:10.1038/s41419-021-04121-9 · Cited by 131 · see citing works
“Further, we used the “autophagy core” list for gene set enrichment analysis by means of the published RNA-sequencing (RNA-seq) dataset, performed on starved cells [31] or on Down syndrome primary fibroblasts, in which it has been reported an mTORC1 hyperactivation associated to inhibition of autophagy induction [27],…”
MethodArchaeal Histone Contributions to the Origin of Eukaryotes
Brunk, C. F., & Martin, W. F. (2019) · Trends in Microbiology · doi:10.1016/j.tim.2019.04.002 · Cited by 55 · see citing works
- Authors
- 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.
- Affiliations
- Utrecht University (NL)
- University Medical Center Groningen (NL)
- Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Division of Pediatrics, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- ORCID
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2018-09-11
- Volume
- 15
- Issue
- 1
- Pages
- 98-112
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC6287694
- OpenAlex
- W2889269873
- Cited by
- 55
- References
- 4
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 4 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 1 · 2019: 8
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Autophagy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Figshare (submittedVersion, cc-by)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-nd)
- Figshare (cc-by)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (022.004.018, 91615113)
- Marie Skłodowska-Curie Cofund (713660)
- Marie Skłodowska-Curie ITN (765912)
- Reumafonds (14-3-201)
- ZonMw (016.130.606)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- nutrient deprivation, epigenetic regulation, H3K4me3, H3K27ac, EGR1, autophagic flux, autophagy regulators, transcriptional regulation
- MeSH terms
- Nutrients, Autophagy, Gene Expression Regulation, Humans, Lysosomes, Gene Expression Profiling, Epigenesis, Genetic, Early Growth Response Protein 1, HEK293 Cells
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