PXD015672

PXD015672 is an original dataset announced via ProteomeXchange.

Title	Histone demethylase JMJD3 is a key epigenetic activator of FGF21 signaling-induced hepatic autophagy and lipolysis
Description	Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of autophagy gene transcription remains unclear. Here, we identify Jumonji-D3 (JMJD3/KDM6B) histone demethylase as a key epigenetic activator of hepatic autophagy. Upon fasting-induced fibroblast growth factor-21 (FGF21) signaling, JMJD3 epigenetically upregulated global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increased its nuclear localization and interaction with the nuclear receptor PPARto transcriptionally activate autophagy. Chronic administration of FGF21 in obese mice improved defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and KL were substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_14:35:14.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	PETER YAU
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-02 01:12:10	ID requested
⏵ 1	2020-05-26 14:35:15	announced

Byun S, Seok S, Kim YC, Zhang Y, Yau P, Iwamori N, Xu HE, Ma J, Kemper B, Kemper JK, Fasting-induced FGF21 signaling activates hepatic autophagy and lipid degradation via JMJD3 histone demethylase. Nat Commun, 11(1):807(2020) [pubmed]

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: Mouse, Histone demethylase JMJD3, FGF21, Autophagy, Lypolysis

Jongsook Kim Kemper
contact affiliation	Department of Molecular Integrative Physiology University of Illinois at Urbana/Champaign Urbana, IL 61801
contact email	jongsook@illinois.edu
lab head
PETER YAU
contact affiliation	University of Illinois at Urbana/Champaign
contact email	pmyau@illinois.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015672
     1. Label: PRIDE project
     2. Name: Histone demethylase JMJD3 is a key epigenetic activator of FGF21 signaling-induced hepatic autophagy and lipolysis