PXD040086

PXD040086 is an original dataset announced via ProteomeXchange.

Title	Contrasting effects of whole-body and hepatocyte-specific deletion of the RNA polymerase III repressor Maf1 in the mouse
Description	The conserved phosphoprotein MAF1 is the main known direct repressor of RNA polymerase III (Pol III). MAF1 is phosphorylated and inactivated by the nutrient-sensing TORC1 kinase, making MAF1 a nutrient effector for Pol III transcription. MAF1 has been associated with lipid metabolism in D. melanogaster, C. elegans, and the mouse. However, whereas downregulation of Maf1 generally increases lipogenesis, Maf1-/- mice are lean even under a High Fat (HF) diet. Here we compared Maf1-/- mice fed a Chow diet with mice lacking Maf1 specifically in hepatocytes (Maf1hep-/- mice) fed either a Chow or HF diet. Unlike Maf1-/- mice, Maf1hep-/- mice become slightly heavier than control mice at an old age and much earlier under a HF diet, with increased adiposity. Liver ChIPseq, RNAseq and proteomics analyses indicate increased Pol III occupancy at Pol III genes, very few differences in mRNA accumulation, and subtle changes in protein accumulation that are consistent with increased lipogenesis. RNAseq and metabolite profiling indicate that liver phenotypes of Maf1-/- mice are strongly influenced by systemic inter-organ communication. Notable changes observed in the three phenotypically distinct cohorts include downregulation of Mouse Urinary Proteins, upregulation of Cyp2a4 expression, suggestive of an alteration of Growth Hormone levels or secretion pattern, and downregulation of Angiogenin, a phenomenon that might be directly linked to increased Pol III occupancy of tRNA genes in the main Angiogenin promoter region.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:16:09.061.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Patrice Waridel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-13 01:27:19	ID requested
1	2023-11-28 02:59:12	announced
⏵ 2	2024-10-22 06:16:09	announced	2024-10-22: Updated project metadata.

10.3389/FMOLB.2023.1297800;

submitter keyword: RNA polymerase III, transcription repressor, Maf1, hepatocyte, mouse, metabolic regulation

Nouria Hernandez
contact affiliation	Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne
contact email	Nouria.Hernandez@unil.ch
lab head
Patrice Waridel
contact affiliation	University of Lausanne
contact email	patrice.waridel@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040086
     1. Label: PRIDE project
     2. Name: Contrasting effects of whole-body and hepatocyte-specific deletion of the RNA polymerase III repressor Maf1 in the mouse