Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approach

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interact with the estrogen receptor (ER), thereby disrupting estrogen-mediated signaling. In a previous study, we employed a bioluminescence resonance energy transfer (BRET) system to assess ER dimerization for detecting EDCs. To fur...

Full description

Saved in:
Bibliographic Details
Main Authors: Soomin Yum, Haksoo Lee, Yong-Kook Kwon, Gunyoung Lee, Hye-Young Lee, HyeSook Youn, BuHyun Youn
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Animal Cells and Systems
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19768354.2025.2481984
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849698060340297728
author Soomin Yum
Haksoo Lee
Yong-Kook Kwon
Gunyoung Lee
Hye-Young Lee
HyeSook Youn
BuHyun Youn
author_facet Soomin Yum
Haksoo Lee
Yong-Kook Kwon
Gunyoung Lee
Hye-Young Lee
HyeSook Youn
BuHyun Youn
author_sort Soomin Yum
collection DOAJ
description Endocrine-disrupting chemicals (EDCs) are exogenous compounds that interact with the estrogen receptor (ER), thereby disrupting estrogen-mediated signaling. In a previous study, we employed a bioluminescence resonance energy transfer (BRET) system to assess ER dimerization for detecting EDCs. To further determine whether the BRET assay could be used independently to identify EDCs, we investigated ER-EDC interactions before and after dimerization. Results from isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) revealed that ER dimerization can be mediated by EDCs. Consequently, the BRET assay proved effective in detecting dimerization and clarifying its relevance to EDC-induced signaling disruption. Additionally, to examine EDC-induced transcriptional changes, we performed chromatin immunoprecipitation sequencing (ChIP-seq), followed by gene ontology (GO) analysis. These analyses demonstrated that EDCs affect various signaling pathways, including those involved in antibody-dependent cytotoxicity, bone morphogenetic protein (BMP) signaling in cardiac induction, and hepatocyte growth factor receptor signaling. Overall, this study elucidates the molecular mechanisms by which EDCs influence ER dimerization and signaling. These findings highlight the utility of the BRET-based assay for EDC detection and contribute to a deeper understanding of the systemic effects of EDCs on endocrine disruption.
format Article
id doaj-art-8dd23dca89fe49f0861437ef560eea12
institution DOAJ
issn 1976-8354
2151-2485
language English
publishDate 2025-12-01
publisher Taylor & Francis Group
record_format Article
series Animal Cells and Systems
spelling doaj-art-8dd23dca89fe49f0861437ef560eea122025-08-20T03:19:02ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852025-12-0129128229510.1080/19768354.2025.2481984Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approachSoomin Yum0Haksoo Lee1Yong-Kook Kwon2Gunyoung Lee3Hye-Young Lee4HyeSook Youn5BuHyun Youn6Department of Integrated Biological Science, Pusan National University, Kumjeong-ku, Republic of KoreaDepartment of Integrated Biological Science, Pusan National University, Kumjeong-ku, Republic of KoreaFood Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation, Cheongju-si, Republic of KoreaFood Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation, Cheongju-si, Republic of KoreaFood Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation, Cheongju-si, Republic of KoreaDepartment of Integrative Bioscience and Biotechnology, Sejong University, Seoul, Republic of KoreaDepartment of Integrated Biological Science, Pusan National University, Kumjeong-ku, Republic of KoreaEndocrine-disrupting chemicals (EDCs) are exogenous compounds that interact with the estrogen receptor (ER), thereby disrupting estrogen-mediated signaling. In a previous study, we employed a bioluminescence resonance energy transfer (BRET) system to assess ER dimerization for detecting EDCs. To further determine whether the BRET assay could be used independently to identify EDCs, we investigated ER-EDC interactions before and after dimerization. Results from isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) revealed that ER dimerization can be mediated by EDCs. Consequently, the BRET assay proved effective in detecting dimerization and clarifying its relevance to EDC-induced signaling disruption. Additionally, to examine EDC-induced transcriptional changes, we performed chromatin immunoprecipitation sequencing (ChIP-seq), followed by gene ontology (GO) analysis. These analyses demonstrated that EDCs affect various signaling pathways, including those involved in antibody-dependent cytotoxicity, bone morphogenetic protein (BMP) signaling in cardiac induction, and hepatocyte growth factor receptor signaling. Overall, this study elucidates the molecular mechanisms by which EDCs influence ER dimerization and signaling. These findings highlight the utility of the BRET-based assay for EDC detection and contribute to a deeper understanding of the systemic effects of EDCs on endocrine disruption.https://www.tandfonline.com/doi/10.1080/19768354.2025.2481984Estrogen receptor signalingbioluminescence resonance energy transfer (BRET)endocrine-disrupting chemicals (EDCs)estrogen receptor dimerizationendocrine disruption mechanism
spellingShingle Soomin Yum
Haksoo Lee
Yong-Kook Kwon
Gunyoung Lee
Hye-Young Lee
HyeSook Youn
BuHyun Youn
Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approach
Animal Cells and Systems
Estrogen receptor signaling
bioluminescence resonance energy transfer (BRET)
endocrine-disrupting chemicals (EDCs)
estrogen receptor dimerization
endocrine disruption mechanism
title Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approach
title_full Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approach
title_fullStr Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approach
title_full_unstemmed Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approach
title_short Unraveling ER dimerization dynamics in endocrine disruption based on a BRET-focused approach
title_sort unraveling er dimerization dynamics in endocrine disruption based on a bret focused approach
topic Estrogen receptor signaling
bioluminescence resonance energy transfer (BRET)
endocrine-disrupting chemicals (EDCs)
estrogen receptor dimerization
endocrine disruption mechanism
url https://www.tandfonline.com/doi/10.1080/19768354.2025.2481984
work_keys_str_mv AT soominyum unravelingerdimerizationdynamicsinendocrinedisruptionbasedonabretfocusedapproach
AT haksoolee unravelingerdimerizationdynamicsinendocrinedisruptionbasedonabretfocusedapproach
AT yongkookkwon unravelingerdimerizationdynamicsinendocrinedisruptionbasedonabretfocusedapproach
AT gunyounglee unravelingerdimerizationdynamicsinendocrinedisruptionbasedonabretfocusedapproach
AT hyeyounglee unravelingerdimerizationdynamicsinendocrinedisruptionbasedonabretfocusedapproach
AT hyesookyoun unravelingerdimerizationdynamicsinendocrinedisruptionbasedonabretfocusedapproach
AT buhyunyoun unravelingerdimerizationdynamicsinendocrinedisruptionbasedonabretfocusedapproach