A CRISPR-based high-throughput screening system identifies bromodomain inhibitors as transcriptional suppressors of CYP11B1 Article Swipe
Ryo Ito
,
Taichi Nakano
,
Akira Sugawara
,
Atsushi Yokoyama
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.bbrc.2025.151779
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.bbrc.2025.151779
CYP11B1 encodes steroid 11β-hydroxylase, the final rate-limiting enzyme for cortisol biosynthesis in the adrenal cortex. Excessive cortisol production is a hallmark of Cushing's disease (CD). While direct enzymatic inhibitors have been explored, achieving specificity remains a challenge due to the high homology between CYP11B1 and CYP11B2, highlighting transcriptional suppression of CYP11B1 as an alternative therapeutic strategy. To identify transcriptional regulators of CYP11B1, we generated genome-edited H295R adrenal cells carrying a luciferase reporter knocked into the endogenous CYP11B1 locus. Using this reporter cell line, we established a high-throughput screening (HTS) platform and screened a focused chemical library targeting epigenetic-related factors, given the importance of epigenetic mechanisms in gene regulation. Among eight candidate compounds identified, we focused on JQ1, a bromodomain inhibitor. JQ1 significantly suppressed Forskolin-induced CYP11B1 promoter activity and mRNA expression without causing cytotoxicity, suggesting the involvement of epigenetic readers in the transcriptional regulation of steroidogenic genes. Furthermore, the reporter-based HTS platform developed here, when combined with our previously established CYP11B2-luciferase system, may facilitate the identification of compounds that selectively modulate adrenal steroidogenic pathways. These findings provide a foundation for the development of novel transcription-targeted therapies for CD.
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Metadata
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- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.bbrc.2025.151779
- OA Status
- hybrid
- Cited By
- 1
- References
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- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4409253178Canonical identifier for this work in OpenAlex
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https://doi.org/10.1016/j.bbrc.2025.151779Digital Object Identifier
- Title
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A CRISPR-based high-throughput screening system identifies bromodomain inhibitors as transcriptional suppressors of CYP11B1Work title
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-04-08Full publication date if available
- Authors
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Ryo Ito, Taichi Nakano, Akira Sugawara, Atsushi YokoyamaList of authors in order
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https://doi.org/10.1016/j.bbrc.2025.151779Publisher landing page
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://doi.org/10.1016/j.bbrc.2025.151779Direct OA link when available
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CRISPR, Bromodomain, Computational biology, Biology, High-throughput screening, Suppressor, Throughput, Genetics, Computer science, Epigenetics, Gene, Wireless, TelecommunicationsTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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