PXD031617

PXD031617 is an original dataset announced via ProteomeXchange.

Title	Histone H4K20 Trimethylation is Decreased in Murine Models of Heart Disease
Description	Heart disease is the leading cause of death in the developed world, and its comorbidities such as hypertension, diabetes, and heart failure are accompanied by major transcriptomic changes in the heart. During cardiac dysfunction, which leads to heart failure, there are global epigenetic alterations to chromatin that occur concomitantly with morphological changes in the heart in response to acute and chronic stress. These epigenetic alterations include the reversible methylation of lysine residues on histone proteins. Lysine methylation on histone H3K4 and H3K9 were among the first methylated lysine residues identified and have been linked to gene activation and silencing, respectively. However, much less is known regarding other methylated histone residues, including histone H4K20. Trimethylation of histone H4K20 has been shown to repressive gene expression, however this mark has never been examined in the heart. Here we utilized immunoblotting and mass spectrometry to quantify histone H4K20 trimethylation in three models of cardiac dysfunction. Our results show that lysine methylation at this site is regulated in a biphasic manner leading to increased H420 trimethylation during acute hypertrophic stress and decreased H4K20 trimethylation during sustained ischemic injury and cardiac dysfunction. In addition, we examined publicly available datasets to analyze enzymes that regulate H4K20 methylation and identified one demethylase (KDM7C) and two methyltransferases (KMT5A and SMYD5) which were all upregulated in heart failure patients. This is the first study to examine histone H4K20 trimethylation in the heart and to determine how this post-translational modification is differentially regulated in multiple models of cardiac disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:34:35.162.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ryan Bia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-11 06:28:04	ID requested
1	2022-10-14 12:09:55	announced
⏵ 2	2023-11-14 07:34:37	announced	2023-11-14: Updated project metadata.

Hickenlooper SM, Davis K, Szulik MW, Sheikh H, Miller M, Valdez S, Bia R, Franklin S, Histone H4K20 Trimethylation Is Decreased in Murine Models of Heart Disease. ACS Omega, 7(35):30710-30719(2022) [pubmed]

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

submitter keyword: Mouse, SHAM, Lysate, LVAD, WT, PO

Sarah Franklin
contact affiliation	Principal Investigator
contact email	sarah.franklin@utah.edu
lab head
Ryan Bia
contact affiliation	University of Utah
contact email	ryan.bia@utah.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031617
     1. Label: PRIDE project
     2. Name: Histone H4K20 Trimethylation is Decreased in Murine Models of Heart Disease