Proteomics

Dataset Information

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Large scale toxicoepigenetics on histones: a mass spectrometry-based screening assay applied to developmental toxicity


ABSTRACT: 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.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human) Bos Taurus (bovine)

TISSUE(S): Cell Culture, Embryonic Stem Cell

SUBMITTER: Maarten Dhaenens  

LAB HEAD: Maarten Dhaenens

PROVIDER: PXD026468 | Pride | 2022-02-17

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
200422_LDC_SV_DDA_PenG_5000A.wiff Wiff
200422_LDC_SV_DDA_PenG_5000A.wiff.scan Wiff
200422_LDC_SV_DDA_PenG_5000B.wiff Wiff
200422_LDC_SV_DDA_PenG_5000B.wiff.scan Wiff
200422_LDC_SV_DDA_PenG_5000C1.wiff Wiff
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Publications

A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity.

Verhelst Sigrid S   Van Puyvelde Bart B   Willems Sander S   Daled Simon S   Cornelis Senne S   Corveleyn Laura L   Willems Ewoud E   Deforce Dieter D   De Clerck Laura L   Dhaenens Maarten M  

Scientific reports 20220124 1


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 promising and 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 to  ...[more]

Publication: 1/2

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