Systemic approaches using single cell transcriptome reveal that C/EBP gamma regulates autophagy under amino acid starved conditionopen access
- Authors
- Kim, Dongha; Kim, Junil; Yu, Young Suk; Kim, Yong Ryoul; Baek, Sung Hee; Won, Kyoung-Jae
- Issue Date
- Jul-2022
- Publisher
- OXFORD UNIV PRESS
- Citation
- NUCLEIC ACIDS RESEARCH, v.50, no.13, pp.7298 - 7309
- Journal Title
- NUCLEIC ACIDS RESEARCH
- Volume
- 50
- Number
- 13
- Start Page
- 7298
- End Page
- 7309
- URI
- http://scholarworks.bwise.kr/ssu/handle/2018.sw.ssu/43620
- DOI
- 10.1093/nar/gkac593
- ISSN
- 0305-1048
- Abstract
- Autophagy, a catabolic process to remove unnecessary or dysfunctional organelles, is triggered by various signals including nutrient starvation. Depending on the types of the nutrient deficiency, diverse sensing mechanisms and signaling pathways orchestrate for transcriptional and epigenetic regulation of autophagy. However, our knowledge about nutrient type-specific transcriptional regulation during autophagy is limited. To understand nutrient type-dependent transcriptional mechanisms during autophagy, we performed single cell RNA sequencing (scRNAseq) in the mouse embryonic fibroblasts (MEFs) with or without glucose starvation (GS) as well as amino acid starvation (AAS). Trajectory analysis using scRNAseq identified sequential induction of potential transcriptional regulators for each condition. Gene regulatory rules inferred using TENET newly identified CCAAT/enhancer binding protein gamma (C/EBP gamma) as a regulator of autophagy in AAS, but not GS, condition, and knockdown experiment confirmed the TENET result. Cell biological and biochemical studies validated that activating transcription factor 4 (ATF4) is responsible for conferring specificity to C/EBP gamma for the activation of autophagy genes under AAS, but not under GS condition. Together, our data identified C/EBP gamma as a previously unidentified key regulator under AAS-induced autophagy.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Natural Sciences > School of Systems and Biomedical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.