PXD012640

PXD012640 is an original dataset announced via ProteomeXchange.

Title	Systematic genome perturbation reveals coordination of lipid droplets and metabolic gene regulation
Description	Lipid droplets (LDs) store lipids for metabolic eneergy and are central to cellular lipid homeostasis. The mechanisms coordinating lipid storage in LDs with cellular metabolism are unclear but relevant to obesity-related diseases. Here we utilized genome-wide screening to identify genes that modulate lipid storage in human macrophages, a cell type relevant to metabolic diseases. Among ~550 genes regulating lipid storage, we identify MLX, a basic helix-loop-helix leucine-zipper transcription factor that regulates multiple metabolic processes. We show that MLX and family members MLXIP/MondoA and MLXIPL/ChREBP bind LDs via C-terminal amphipathic helices. When LDs increase in cells, LD binding of MLX, MLXIP/MondoA, and MLXIPL/ChREBP reduces their transcriptional activity, whereas the absence of LDs results in hyperactivation. Our findings uncover an unexpected component to a lipid storage response, in which binding of MLX transcription factors to the LD surface modulates their activity, adjusting the expression of metabolic genes to lipid storage levels.
HostingRepository	PRIDE
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_08:57:07.627.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zon Lai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-08 02:40:24	ID requested
⏵ 1	2021-09-08 08:57:08	announced

Mejhert N, Kuruvilla L, Gabriel KR, Elliott SD, Guie MA, Wang H, Lai ZW, Lane EA, Christiano R, Danial NN, Farese RV, Walther TC, Partitioning of MLX-Family Transcription Factors to Lipid Droplets Regulates Metabolic Gene Expression. Mol Cell, 77(6):1251-1264.e9(2020) [pubmed]

submitter keyword: ChREBP, glucose, lipid droplets, metabolism, MLX, MLXIP, MLXIPL, MondoA, MondoB, transcription facot

Tobias Walther
contact affiliation	Harvard School of Public Health
contact email	twalther@hsph.harvard.edu
lab head
Zon Lai
contact affiliation	Harvard T. H. Chan School of Public Health
contact email	zlai@hsph.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012640
     1. Label: PRIDE project
     2. Name: Systematic genome perturbation reveals coordination of lipid droplets and metabolic gene regulation