A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity
- Author
- Sigrid Verhelst (UGent) , Bart Van Puyvelde (UGent) , Sander Willems, Simon Daled (UGent) , Senne Cornelis (UGent) , Laura Corveleyn (UGent) , Ewoud Willems, Dieter Deforce (UGent) , Laura De Clerck (UGent) and Maarten Dhaenens (UGent)
- Organization
- Project
-
- Volgen van de wijzigingen in het histon-modificatiepatroon met niet-gerichte massaspectrometrie
- High throughput MS-based histone PTM screening: Filling a void in pharmacoepigenetics.
- Data Independent Acquisition Mass Spectrometry to Mine Human Stem Cell Histone Epigenetics
- Data Independent Acquisition Mass Spectrometry to Mine Human Stem Cell Histone Epigenetics
- Ion mobility assisted Data Independent Acquisition of the histone code: opening up peptide-centric data mining.
- Histone epigenetic profiling in pharmaco- and toxicoepigenetics.
- 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 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 toxicity testing, especially for developmental toxicity. Consequently, we developed a mass spectrometry-based proof-of-concept to assess a histone code screening assay capable of simultaneously detecting multiple hPTM-changes in human embryonic stem cells. We first validated the untargeted workflow with valproic acid (VPA), a histone deacetylase inhibitor. These results demonstrate the capability of mapping the hPTM-dynamics, with a general increase in acetylations as an internal control. To illustrate the scalability, a dose–response study was performed on a proof-of-concept library of ten compounds (1) with a known effect on the hPTMs (BIX-01294, 3-Deazaneplanocin A, Trichostatin A, and VPA), (2) classified as highly embryotoxic by the European Centre for the Validation of Alternative Methods (ECVAM) (Methotrexate, and All-trans retinoic acid), (3) classified as non-embryotoxic by ECVAM (Penicillin G), and (4) compounds of abuse with a presumed developmental toxicity (ethanol, caffeine, and nicotine).
- Keywords
- LC-MS/MS, toxicoepigenetics, histone post-translational modifications, developmental toxicity, EMBRYONIC STEM-CELLS, VALPROIC ACID, ENVIRONMENTAL CHEMICALS, GENE-EXPRESSION, RETINOIC ACID, METHYLATION, NICOTINE, DIFFERENTIATION, DEACETYLASE, ASSAY
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8735551
- MLA
- Verhelst, Sigrid, et al. “A Large Scale Mass Spectrometry-Based Histone Screening for Assessing Epigenetic Developmental Toxicity.” SCIENTIFIC REPORTS, vol. 12, no. 1, 2022, doi:10.1038/s41598-022-05268-x.
- APA
- Verhelst, S., Van Puyvelde, B., Willems, S., Daled, S., Cornelis, S., Corveleyn, L., … Dhaenens, M. (2022). A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity. SCIENTIFIC REPORTS, 12(1). https://doi.org/10.1038/s41598-022-05268-x
- Chicago author-date
- Verhelst, Sigrid, Bart Van Puyvelde, Sander Willems, Simon Daled, Senne Cornelis, Laura Corveleyn, Ewoud Willems, Dieter Deforce, Laura De Clerck, and Maarten Dhaenens. 2022. “A Large Scale Mass Spectrometry-Based Histone Screening for Assessing Epigenetic Developmental Toxicity.” SCIENTIFIC REPORTS 12 (1). https://doi.org/10.1038/s41598-022-05268-x.
- Chicago author-date (all authors)
- Verhelst, Sigrid, Bart Van Puyvelde, Sander Willems, Simon Daled, Senne Cornelis, Laura Corveleyn, Ewoud Willems, Dieter Deforce, Laura De Clerck, and Maarten Dhaenens. 2022. “A Large Scale Mass Spectrometry-Based Histone Screening for Assessing Epigenetic Developmental Toxicity.” SCIENTIFIC REPORTS 12 (1). doi:10.1038/s41598-022-05268-x.
- Vancouver
- 1.Verhelst S, Van Puyvelde B, Willems S, Daled S, Cornelis S, Corveleyn L, et al. A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity. SCIENTIFIC REPORTS. 2022;12(1).
- IEEE
- [1]S. Verhelst et al., “A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity,” SCIENTIFIC REPORTS, vol. 12, no. 1, 2022.
@article{8735551,
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 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 toxicity testing, especially for developmental toxicity. Consequently, we developed a mass spectrometry-based proof-of-concept to assess a histone code screening assay capable of simultaneously detecting multiple hPTM-changes in human embryonic stem cells. We first validated the untargeted workflow with valproic acid (VPA), a histone deacetylase inhibitor. These results demonstrate the capability of mapping the hPTM-dynamics, with a general increase in acetylations as an internal control. To illustrate the scalability, a dose–response study was performed on a proof-of-concept library of ten compounds (1) with a known effect on the hPTMs (BIX-01294, 3-Deazaneplanocin A, Trichostatin A, and VPA), (2) classified as highly embryotoxic by the European Centre for the Validation of Alternative Methods (ECVAM) (Methotrexate, and All-trans retinoic acid), (3) classified as non-embryotoxic by ECVAM (Penicillin G), and (4) compounds of abuse with a presumed developmental toxicity (ethanol, caffeine, and nicotine).}},
articleno = {{1256}},
author = {{Verhelst, Sigrid and Van Puyvelde, Bart and Willems, Sander and Daled, Simon and Cornelis, Senne and Corveleyn, Laura and Willems, Ewoud and Deforce, Dieter and De Clerck, Laura and Dhaenens, Maarten}},
issn = {{2045-2322}},
journal = {{SCIENTIFIC REPORTS}},
keywords = {{LC-MS/MS,toxicoepigenetics,histone post-translational modifications,developmental toxicity,EMBRYONIC STEM-CELLS,VALPROIC ACID,ENVIRONMENTAL CHEMICALS,GENE-EXPRESSION,RETINOIC ACID,METHYLATION,NICOTINE,DIFFERENTIATION,DEACETYLASE,ASSAY}},
language = {{eng}},
number = {{1}},
pages = {{16}},
title = {{A large scale mass spectrometry-based histone screening for assessing epigenetic developmental toxicity}},
url = {{http://doi.org/10.1038/s41598-022-05268-x}},
volume = {{12}},
year = {{2022}},
}
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