SAMS-1 coordinates HLH-30/TFEB and PHA-4/FOXA activities through histone methylation to mediate dietary restriction-induced autophagy and longevity. Issue 1 (2nd January 2023)

• Record Type: Journal Article
• Authors: Lim, Chiao-Yin; Lin, Huan-Ting; Kumsta, Caroline; Lu, Tzu-Chiao; Wang, Feng-Yung; Kang, Yun-Hsuan; Hansen, Malene; Ching, Tsui-Ting; Hsu, Ao-Lin
• Is Part Of: Autophagy. Volume 19:Issue 1(2023)
• Page Start: 224
• Page End: 240
• Publication Date: 2023-01-02
• Subjects: Aging -- Caenorhabditis. elegans -- dietary restriction -- histone methylation -- HLH-30/TFEB -- PHA-4/FOXA -- S-adenosyl methionine -- SET-2 histone methyltransferase; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2022.2068267
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: Dietary restriction (DR) is known to promote autophagy to exert its longevity effect. While SAMS-1 (S-adenosyl methionine synthetase-1) has been shown to be a key mediator of the DR response, little is known about the roles of S-adenosyl methionine (SAM) and SAM-dependent methyltransferase in autophagy and DR-induced longevity. In this study, we show that DR and SAMS-1 repress the activity of SET-2, a histone H3K4 methyltransferase, by limiting the availability of SAM. Consequently, the reduced H3K4me3 levels promote the expression and activity of two transcription factors, HLH-30/TFEB and PHA-4/FOXA, which both regulate the transcription of autophagy-related genes. We then find that HLH-30/TFEB and PHA-4/FOXA act collaboratively on their common target genes to mediate the transcriptional response of autophagy-related genes and consequently the lifespan of the animals. Our study thus shows that the SAMS-1-SET-2 axis serves as a nutrient-sensing module to epigenetically coordinate the activation of HLH-30/TFEB and PHA-4/FOXA transcription factors to control macroautophagy/autophagy and longevity in response to DR. Abbreviations: ChIP: chromatin immunoprecipitation; ChIP-seq: chromatin immuno precipitation-sequencing; COMPASS: complex of proteins associated with Set1; DR: dietary restriction; GO: gene ontology; SAM: S-adenosyl methionine; SAMS-1: S-adenosyl methionine synthetase-1; TSS: transcription start site; WT: wild-type.