PXD042624

PXD042624 is an original dataset announced via ProteomeXchange.

Title	Multi-acetylated histones are a source of carbon for lipid synthesis
Description	Histone modifications commonly integrate environmental stimuli to cellular metabolic outputs by affecting gene expression. Many modifications, including some histone acetylation marks, do not always correlate to transcription, thus pointing towards an alternative role of histone modifications as potential metabolic reservoirs. Using an approach that integrates mass spectrometry- based epi-proteomics and metabolomics with stable isotope tracer studies, we demonstrate that elevated lipids in histone acetyltransferase (HAT)-depleted hepatocytes result from carbon atoms flowing from the deacetylation of multi-acetylated histone H4 to fatty acids. Consistent with this, the enhanced lipid synthesis in HAT-depleted hepatocytes is dependent on the activity of histone deacetylases (HDACs) and acetyl-CoA synthetase ACSS2. Furthermore, we show that during diet-induced lipid synthesis there is a reduction of multi-acetylated histone H4 in hepatocytes and in mouse liver. In addition, overexpression of histone acetyltransferases can reverse diet-induced lipogenesis by blocking lipid droplet accumulation and maintaining the levels of multi-acetylated histone H4. This study unveils an additional link between epigenetics and metabolism whereby histone acetylation reservoirs may serve as a carbon source for lipid synthesis.
HostingRepository	PRIDE
AnnounceDate	2024-02-14
AnnouncementXML	Submission_2024-02-14_05:36:16.961.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Roberta Noberini
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive HF; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-01 10:13:58	ID requested
⏵ 1	2024-02-14 05:36:17	announced

10.1038/S44318-024-00053-0;

submitter keyword: metabolism,histone post-translational modifications

Tiziana Bonaldi
contact affiliation	European Institute of Oncology
contact email	tiziana.bonaldi@ieo.it
lab head
Roberta Noberini
contact affiliation	Istituto Europeo di Oncologia
contact email	roberta.noberini@ieo.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042624
     1. Label: PRIDE project
     2. Name: Multi-acetylated histones are a source of carbon for lipid synthesis