气候变化领域集成服务门户(CCPortal): Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions

CCPortal

DOI	10.1073/pnas.2104832118
	Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions
	Mony V.K.; Drangowska-Way A.; Albert R.; Harrison E.; Ghaddar A.; Horak M.K.; Ke W.; O’Rourke E.J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:41
英文摘要	Plasticity in multicellular organisms involves signaling pathways converting contexts—either natural environmental challenges or laboratory perturbations—into context-specific changes in gene expression. Congruently, the interactions between the signaling molecules and transcription factors (TF) regulating these responses are also context specific. However, when a target gene responds across contexts, the upstream TF identified in one context is often inferred to regulate it across contexts. Reconciling these stable TF–target gene pair inferences with the context-specific nature of homeostatic responses is therefore needed. The induction of the Caenorhabditis elegans genes lipl-3 and lipl-4 is observed in many genetic contexts and is essential to survival during fasting. We find DAF-16/FOXO mediating lipl-4 induction in all contexts tested; hence, lipl-4 regulation seems context independent and compatible with across-context inferences. In contrast, DAF-16–mediated regulation of lipl-3 is context specific. DAF-16 reduces the induction of lipl-3 during fasting, yet it promotes it during oxidative stress. Through discrete dynamic modeling and genetic epistasis, we define that DAF-16 represses HLH-30/TFEB—the main TF activating lipl-3 during fasting. Contrastingly, DAF-16 activates the stress-responsive TF HSF-1 during oxidative stress, which promotes C. elegans survival through induction of lipl-3. Furthermore, the TF MXL-3 contributes to the dominance of HSF-1 at the expense of HLH-30 during oxidative stress but not during fasting. This study shows how context-specific diverting of functional interactions within a molecular network allows cells to specifically respond to a large number of contexts with a limited number of molecular players, a mode of transcriptional regulation we name “contextualized transcription.”. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Fasting; Fat; FOXO/DAF-16; Oxidative stress; TFEB/HLH-30
语种	英语
scopus关键词	basic helix loop helix transcription factor; Caenorhabditis elegans protein; daf-16 protein, C elegans; forkhead transcription factor; heat shock factor-1, C elegans; HLH-30 protein, C elegans; LIPL-4 protein, C elegans; MXL-3 protein, C elegans; transcription factor; triacylglycerol lipase; animal; Caenorhabditis elegans; diet restriction; gene expression regulation; genetic transcription; genetics; lipolysis; metabolism; oxidative stress; physiology; signal transduction; transcription initiation; Animals; Basic Helix-Loop-Helix Transcription Factors; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Fasting; Forkhead Transcription Factors; Gene Expression Regulation; Lipase; Lipolysis; Oxidative Stress; Signal Transduction; Transcription Factors; Transcription, Genetic; Transcriptional Activation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251007
作者单位	Department of Biology, University of Virginia, Charlottesville, VA 22903, United States; Department of Physics, Pennsylvania State University, University Park, PA 16801, United States; Department of Cell Biology, University of Virginia, Charlottesville, VA 22903, United States; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22903, United States
推荐引用方式 GB/T 7714	Mony V.K.,Drangowska-Way A.,Albert R.,et al. Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions[J],2021,118(41).
APA	Mony V.K..,Drangowska-Way A..,Albert R..,Harrison E..,Ghaddar A..,...&O’Rourke E.J..(2021).Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions.Proceedings of the National Academy of Sciences of the United States of America,118(41).
MLA	Mony V.K.,et al."Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions".Proceedings of the National Academy of Sciences of the United States of America 118.41(2021).