PXD026468

PXD026468 is an original dataset announced via ProteomeXchange.

Title	Large scale toxicoepigenetics on histones: a mass spectrometry-based screening assay applied to developmental toxicity
Description	Toxicoepigenetics is an emerging field that studies the toxicological impact of compounds on protein expression through heritable, non-genetic mechanisms, such as histone post-translational modifications (hPTMs). Due to substantial progress in the large-scale study of hPTMs, integration into the field of toxicology is a promising addition that offers the opportunity to gain novel insights into toxicological phenomena. Moreover, there is a growing demand for high-throughput human-based in vitro assays for toxicity testing and especially for developmental toxicity. Consequently, we developed a mass spectrometry based proof-of-concept to develop an assay to screen the histone code and hence detecting multiple hPTMs changes simultaneously in human embryonic stem cells. To prove the applicability and performance, we first validated the untargeted workflow with valproic acid (VPA), a histone deacetylase inhibitor. These results demonstrate that our workflow is capable of mapping the hPTM-dynamics, with a general increase in acetylations as an internal control. To illustrate the scalability, the workflow was applied on a proof-of-concept dose-response library of a total of ten compounds with either i) a known effect on the hPTMs (BIX-01294, 3-Deazaneplanocin A, Trichostatin A, and VPA), ii) a presumed developmental toxicity, including compounds of abuse (Caffeine, Ethanol, Nicotine, Methotrexate, and All-trans retinoic acid), or iii) no proven embryotoxicity (Penicillin G). In conclusion, we show that toxicoepigenetic screening on histones is feasible and yields very rich data that holds great potential, not only for applications in the pharmaceutical industry, but also for environmental toxicity and food safety.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:40:44.528.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD026468
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Maarten Dhaenens
SpeciesList	scientific name: Bos taurus (Bovine); NCBI TaxID: 9913; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monomethylated residue; dimethylated L-arginine; crotonylated L-lysine; trimethylated residue; acetylated residue; monohydroxylated residue; formylated residue; deamidated residue; N6,N6-dimethyl-L-lysine
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-03 09:09:15	ID requested
⏵ 1	2024-10-07 13:40:45	announced

Verhelst S, De Clerck L, Willems S, Van Puyvelde B, Daled S, Deforce D, Dhaenens M, Comprehensive histone epigenetics: A mass spectrometry based screening assay to measure epigenetic toxicity. MethodsX, 7():101055(2020) [pubmed]

10.6019/PXD026468;

Verhelst S, Van Puyvelde B, Willems S, Daled S, Cornelis S, Corveleyn L, Willems E, Deforce D, De Clerck L, Dhaenens M, A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity. Sci Rep, 12(1):1256(2022) [pubmed]

10.1016/j.mex.2020.101055;

10.1038/s41598-022-05268-x;

submitter keyword: Histone post-translational modifications, drug screening, toxicoepigenetics, developmental toxicity, LC-MS/MS

Maarten Dhaenens
contact affiliation	ProGenTomics, Laboratory of Pharmaceutical Biotechnology, Ghent University, B-9000 Ghent, Belgium
contact email	maarten.dhaenens@ugent.be
lab head
Maarten Dhaenens
contact affiliation	Faculity of Pharmaceutical Biotechnology
contact email	maarten.dhaenens@ugent.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026468
     1. Label: PRIDE project
     2. Name: Large scale toxicoepigenetics on histones: a mass spectrometry-based screening assay applied to developmental toxicity